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[ "BMC", "Public", "Health", "Research", "article", "Are", "alcoholism", "treatments", "effective?", "The", "Project", "MATCH", "data", "Robert", "B", "Cutler*", "and", "David", "A", "Fishbain", "BioMed", "Central", "Open", "Access", "Address:", "Department", "of", "Psychiatry", "and", "Behavioral", "Sciences,", "University", "of", "Miami", "School", "of", "Medicine,", "Miami,", "Florida,", "USA", "Email:", "Robert", "B", "Cutler*", "-", "r.cutler@miami.edu;", "David", "A", "Fishbain", "-", "d.fishbain@miami.edu", "*", "Corresponding", "author", "Published:", "14", "July", "2005", "BMC", "Public", "Health", "2005,", "5:75", "doi:10.1186/1471-2458-5-75", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2458/5/75", "Received:", "02", "September", "2004", "Accepted:", "14", "July", "2005", "©", "2005", "Cutler", "and", "Fishbain;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Project", "MATCH", "was", "the", "largest", "and", "most", "expensive", "alcoholism", "treatment", "trial", "ever", "conducted.", "The", "results", "were", "disappointing.", "There", "were", "essentially", "no", "patient-treatment", "matches,", "and", "three", "very", "different", "treatments", "produced", "nearly", "identical", "outcomes.", "These", "results", "were", "interpreted", "post", "hoc", "as", "evidence", "that", "all", "three", "treatments", "were", "quite", "effective.", "We", "re-analyzed", "the", "data", "in", "order", "to", "estimate", "effectiveness", "in", "relation", "to", "quantity", "of", "treatment.", "Methods:", "This", "was", "a", "secondary", "analysis", "of", "data", "from", "a", "multisite", "clinical", "trial", "of", "alcohol", "dependent", "volunteers", "(N", "=", "1726)", "who", "received", "outpatient", "psychosocial", "therapy.", "Analyses", "were", "confined", "to", "the", "primary", "outcome", "variables,", "percent", "days", "abstinent", "(PDA)", "and", "drinks", "per", "drinking", "day", "(DDD).", "Overall", "tests", "between", "treatment", "outcome", "and", "treatment", "quantity", "were", "conducted.", "Next,", "three", "specific", "groups", "were", "highlighted.", "One", "group", "consisted", "of", "those", "who", "dropped", "out", "immediately;", "the", "second", "were", "those", "who", "dropped", "out", "after", "receiving", "only", "one", "therapy", "session,", "and", "the", "third", "were", "those", "who", "attended", "12", "therapy", "sessions.", "Results:", "Overall,", "a", "median", "of", "only", "3%", "of", "the", "drinking", "outcome", "at", "follow-up", "could", "be", "attributed", "to", "treatment.", "However", "this", "effect", "appeared", "to", "be", "present", "at", "week", "one", "before", "most", "of", "the", "treatment", "had", "been", "delivered.", "The", "zero", "treatment", "dropout", "group", "showed", "great", "improvement,", "achieving", "a", "mean", "of", "72", "percent", "days", "abstinent", "at", "follow-up.", "Effect", "size", "estimates", "showed", "that", "two-thirds", "to", "three-fourths", "of", "the", "improvement", "in", "the", "full", "treatment", "group", "was", "duplicated", "in", "the", "zero", "treatment", "group.", "Outcomes", "for", "the", "one", "session", "treatment", "group", "were", "worse", "than", "for", "the", "zero", "treatment", "group,", "suggesting", "a", "patient", "self", "selection", "effect.", "Nearly", "all", "the", "improvement", "in", "all", "groups", "had", "occurred", "by", "week", "one.", "The", "full", "treatment", "group", "had", "improved", "in", "PDA", "by", "62%", "at", "week", "one,", "and", "the", "additional", "11", "therapy", "sessions", "added", "only", "another", "4%", "improvement.", "Conclusion:", "The", "results", "suggest", "that", "current", "psychosocial", "treatments", "for", "alcoholism", "are", "not", "particularly", "effective.", "Untreated", "alcoholics", "in", "clinical", "trials", "show", "significant", "improvement.", "Most", "of", "the", "improvement", "which", "is", "interpreted", "as", "treatment", "effect", "is", "not", "due", "to", "treatment.", "Part", "of", "the", "remainder", "appears", "to", "be", "due", "to", "selection", "effects.", "Background", "A", "fundamental", "belief", "of", "addiction", "treatment", "is", "that", "ther-", "apy", "is", "effective.", "Addiction", "counselors", "are", "encouraged", "to", "use", "methods", "that", "have", "been", "shown", "to", "be", "effective", "in", "high", "quality", "clinical", "trials", "[1].", "Three", "of", "the", "best", "of", "those", "meth-", "ods", "were", "selected", "for", "Project", "MATCH,", "a", "large", "multicenter", "US", "trial", "designed", "to", "match", "the", "most", "effective", "treatment", "to", "individual", "patient", "characteristics.", "The", "criteria", "used", "to", "Page", "1", "of", "11", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "JCB", "Article", "Dynamics", "of", "ligand-induced,", "Rac1-dependent", "anchoring", "of", "cadherins", "to", "the", "actin", "cytoskeleton", "Mireille", "Lambert,1", "Daniel", "Choquet,2", "and", "René-Marc", "Mège1", "1Signalisation", "et", "Différenciation", "Cellulaires", "dans", "les", "Systèmes", "Nerveux", "et", "Musculaire,", "INSERM", "U440,", "Université", "Paris", "6,", "Institut", "du", "Fer", "à", "Moulin,", "75005", "Paris,", "France", "2Physiologie", "Cellulaire", "de", "la", "Synapse,", "UMR", "CNRS", "5091-Université", "Bordeaux", "2,", "Institut", "François", "Magendie,", "33077", "Bordeaux", "cedex,", "France", "C", "cules", "during", "development.", "To", "dissect", "their", "mode", "of", "adherin", "receptors", "are", "key", "morphoregulatory", "mole-", "action,", "we", "developed", "an", "approach", "based", "on", "the", "use", "of", "myogenic", "C2", "cells", "and", "beads", "coated", "with", "an", "Ncad-Fc", "ligand,", "allowing", "us", "to", "mimic", "cadherin-mediated", "adhesion.", "We", "used", "optical", "tweezers", "and", "video", "microscopy", "to", "investigate", "the", "dynamics", "of", "N-cadherin", "anchoring", "within", "the", "very", "first", "seconds", "of", "bead–cell", "contact.", "The", "analysis", "of", "the", "bead", "movement", "by", "single-particle", "tracking", "indicated", "that", "N-cadherin", "molecules", "were", "freely", "diffusive", "in", "the", "first", "few", "seconds", "after", "bead", "binding.", "The", "beads", "rapidly", "became", "diffusion-restricted", "and", "underwent", "an", "oriented", "rearward", "movement", "as", "a", "result", "of", "N-cadherin", "anchoring", "to", "the", "actin", "Introduction", "The", "highly", "conserved", "cell", "adhesion", "molecules", "of", "the", "cad-", "herin", "family", "constitute", "one", "of", "the", "major", "classes", "of", "receptors", "mediating", "juxtacrine", "cell", "interactions.", "Cadherins", "are", "key", "morphoregulatory", "molecules", "involved", "in", "developmental", "pro-", "cesses", "(Takeichi,", "1988;", "Yap", "et", "al.,", "1997).", "Their", "contri-", "bution", "to", "cell", "aggregation", "and", "segregation", "is", "essential", "for", "embryogenesis", "and", "histogenesis", "(Friedlander", "et", "al.,", "1989).", "N-cadherin", "is", "involved", "in", "the", "organization", "and", "functional", "regulation", "of", "various", "tissues,", "including", "the", "nervous", "system", "and", "cardiac", "and", "skeletal", "muscles", "(Hatta", "et", "al.,", "1988;", "Radice", "et", "al.,", "1997).", "In", "the", "nervous", "system,", "N-cadherin", "is", "expressed", "in", "a", "combinatorial", "fashion", "with", "other", "members", "of", "the", "cad-", "herin", "family", "throughout", "development,", "and", "is", "thought", "to", "participate", "in", "neuronal", "cell", "sorting", "and", "neurite", "outgrowth,", "as", "well", "as", "synapse", "formation,", "maturation,", "and", "plasticity", "(Benson", "et", "al.,", "2001).", "N-cadherin", "has", "also", "been", "implicated", "in", "myo-", "genic", "precursor", "cell", "migration", "(Brand-Saberi", "et", "al.,", "1996)", "Address", "correspondence", "to", "René-Marc", "Mège,", "INSERM", "U440,", "17", "rue", "du", "Fer", "à", "Moulin,", "75005", "Paris,", "France.", "Tel.:", "33-1-45-87-61-36.", "Fax:", "33-1-", "45-87-61-32.", "E-mail:", "mege@ifm.inserm.fr", "Key", "words:", "cell", "adhesion;", "cytoskeleton;", "signal", "transduction;", "migration;", "mechanotransduction", "", "The", "Rockefeller", "University", "Press,", "0021-9525/2002/04/469/11", "$5.00", "The", "Journal", "of", "Cell", "Biology,", "Volume", "157,", "Number", "3,", "April", "29,", "2002", "469–479", "http://www.jcb.org/cgi/doi/10.1083/jcb.200107104", "cytoskeleton.", "The", "kinetics", "of", "anchoring", "were", "dependent", "on", "ligand", "density,", "suggesting", "that", "it", "was", "an", "inducible", "process", "triggered", "by", "active", "cadherin", "recruitment.", "This", "anchoring", "was", "inhibited", "by", "the", "dominant", "negative", "form", "of", "Rac1,", "but", "not", "that", "of", "Cdc42.", "The", "Rac1", "mutant", "had", "no", "effect", "on", "cell", "contact", "formation", "or", "cadherin–catenin", "complex", "recruitment,", "but", "did", "inhibit", "actin", "recruitment.", "Our", "results", "suggest", "that", "cadherin", "anchoring", "to", "the", "actin", "cytoskeleton", "is", "an", "adhesion-", "triggered,", "Rac1-regulated", "process", "enabling", "the", "transduction", "of", "mechanical", "forces", "across", "the", "cell", "membrane;", "they", "uncover", "novel", "aspects", "of", "the", "action", "of", "cadherins", "in", "cell", "sorting,", "cell", "migration,", "and", "growth", "cone", "navigation.", "and", "differentiation", "(Goichberg", "and", "Geiger,", "1998),", "as", "well", "as", "in", "myoblast", "fusion", "(Mège", "et", "al.,", "1992).", "Cadherins", "are", "transmembrane", "glycoproteins", "that", "mediate", "cell–cell", "adhesion", "through", "homophilic", "Ca2", "-dependent", "in-", "teractions", "of", "their", "extracellular", "region", "and", "anchoring", "of", "their", "intracellular", "domain", "to", "the", "actin", "cytoskeleton", "(Yap", "et", "al.,", "1997).", "Cadherin", "ectodomains", "are", "thought", "to", "dimerize", "and", "to", "interact", "with", "dimers", "of", "the", "same", "cadherin", "species", "at", "the", "surface", "of", "adjacent", "cells", "(Shapiro", "et", "al.,", "1995;", "Pertz", "et", "al.,", "1999).", "On", "the", "other", "hand,", "the", "conserved", "cytoplasmic", "domain", "of", "cadherins", "is", "part", "of", "a", "multimolecular", "complex", "including", "the", "p120", "phosphoprotein", "and", "catenins", "and", ",", "which", "link", "cadherins", "to", "the", "actin", "cytoskeleton", "and", "have", "a", "modulatory", "effect", "on", "cadherin", "adhesive", "function", "(Kemler,", "1993;", "Anasta-", "siadis", "and", "Reynolds,", "2000).", "The", "integrity", "of", "this", "cadherin–", "catenin", "complex", "and", "its", "correct", "association", "to", "the", "actin", "cytoskeleton", "are", "required", "for", "cell", "aggregation", "(Nagafuchi", "and", "Takeichi,", "1988).", "Although", "the", "developmental", "roles", "of", "cadherins", "are", "well", "documented,", "their", "mode", "of", "action", "is", "still", "a", "matter", "of", "intense", "investigation.", "In", "addition", "to", "the", "increasing", "understanding", "of", "the", "molecular", "mechanisms", "underlying", "specific", "adhesive", "in-", "teractions,", "other", "aspects", "(i.e.,", "the", "dynamics", "and", "mechanisms", "469" ]

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[ "4390–4401", "Nucleic", "Acids", "Research,", "2008,", "Vol.", "36,", "No.", "13", "doi:10.1093/nar/gkn400", "Published", "online", "28", "June", "2008", "A", "protein", "functional", "leap:", "how", "a", "single", "mutation", "reverses", "the", "function", "of", "the", "transcription", "regulator", "TetR", "Marcus", "Resch", "1", ",", "Harald", "Striegl1,", "Eva", "Maria", "Henssler2,", "Madhumati", "Sevvana", "1", ",", "Claudia", "Egerer-Sieber1,", "Emile", "Schiltz3,", "Wolfgang", "Hillen2", "and", "Yves", "A.", "Muller1,*", "1Lehrstuhl", "f", "u¨r", "Biotechnik,", "2Lehrstuhl", "f", "u¨r", "Mikrobiologie,", "Department", "of", "Biology,", "Friedrich-Alexander", "University", "Erlangen-Nuremberg,", "Henkestrasse", "91", "and", "Staudtstrasse", "5,", "D-91052", "Erlangen", "and", "3Institut", "fu¨", "r", "Organische", "Chemie", "und", "Biochemie,", "University", "of", "Freiburg,", "Albertstrasse", "21,", "D-79104", "Freiburg,", "Germany", "Received", "March", "20,", "2008;", "Revised", "June", "5,", "2008;", "Accepted", "June", "7,", "2008", "ABSTRACT", "Today’s", "proteome", "is", "the", "result", "of", "innumerous", "gene", "duplication,", "mutagenesis,", "drift", "and", "selection", "pro-", "cesses.", "Whereas", "random", "mutagenesis", "introduces", "predominantly", "only", "gradual", "changes", "in", "protein", "func-", "tion,", "a", "case", "can", "be", "made", "that", "an", "abrupt", "switch", "in", "function", "caused", "by", "single", "amino", "acid", "substitutions", "will", "not", "only", "considerably", "further", "evolution", "but", "might", "constitute", "a", "prerequisite", "for", "the", "appearance", "of", "novel", "functionalities", "for", "which", "no", "promiscuous", "protein", "intermediates", "can", "be", "envisaged.", "Recently,", "tetracy-", "cline", "repressor", "(TetR)", "variants", "were", "identified", "in", "which", "binding", "of", "tetracycline", "triggers", "the", "repressor", "to", "associate", "with", "and", "not", "to", "dissociate", "from", "the", "operator", "DNA", "as", "in", "wild-type", "TetR.", "We", "investigated", "the", "origin", "of", "this", "activity", "reversal", "by", "limited", "prote-", "olysis,", "CD", "spectroscopy", "and", "X-ray", "crystallography.", "We", "show", "that", "the", "TetR", "mutant", "Leu17Gly", "switches", "its", "function", "via", "a", "disorder–order", "mechanism", "that", "differs", "completely", "from", "the", "allosteric", "mechanism", "of", "wild-", "type", "TetR.", "Our", "study", "emphasizes", "how", "single", "point", "mutations", "can", "engender", "unexpected", "leaps", "in", "protein", "function", "thus", "enabling", "the", "appearance", "of", "new", "func-", "tionalities", "in", "proteins", "without", "the", "need", "for", "promiscu-", "ous", "intermediates.", "INTRODUCTION", "Evolution", "is", "considered", "to", "proceed", "through", "countless", "rounds", "of", "random", "mutagenesis", "and", "natural", "selection.", "To", "date,", "a", "wealth", "of", "data", "exist", "showing", "how", "point", "mutations", "gradually", "alter", "protein", "function", "in", "support", "of", "the", "notion", "that", "proteins", "with", "novel", "functions", "are", "the", "result", "of", "an", "evolutionary", "drift", "process", "that", "follows", "an", "initial", "gene", "duplication", "event", "(1,2).", "However,", "as", "a", "consequence", "of", "gene", "duplication,", "protein", "intermediates", "must", "occur", "that", "display", "redundant", "functions.", "Because", "such", "redundancies", "in", "protein", "function", "put", "into", "question", "any", "evolutionary", "advantages", "that", "such", "early", "gene", "duplication", "products", "might", "provide,", "these", "intermediates", "are", "considered", "to", "be", "under", "strong", "purifying", "selection", "with", "the", "conversion", "into", "a", "silenced", "pseudo", "gene", "as", "the", "likely", "outcome", "(3,4).", "In", "this", "context,", "an", "evolutionary", "step,", "in", "which", "random", "mutations", "would", "not", "lead", "to", "a", "gradual", "change", "but", "to", "an", "abrupt", "switch", "in", "function,", "might", "prove", "highly", "advantageous", "as", "a", "poten-", "tial,", "but", "so", "far", "neglected", "silencing", "escape", "mechanism.", "That", "functional", "leaps", "occurred", "during", "evolution", "seems", "obvious", "when", "considering", "evolutionary", "related", "proteins", "with", "functions", "that", "exclude", "each", "other", "and", "for", "which,", "therefore,", "no", "intermediates", "can", "be", "envisaged", "that", "would", "contain", "both", "functionalities.", "The", "bacterial", "repressors", "LacI", "(5)", "and", "PurR", "(6)", "provide", "an", "example", "for", "such", "a", "pair.", "They", "are", "considered", "paralogs", "and", "share", "35%", "sequence", "iden-", "tity", "(7).", "Their", "ability", "to", "bind", "to", "DNA", "is", "modulated", "via", "their", "interaction", "with", "low", "molecular", 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[ "Journal", "of", "Inflammation", "Research", "P38", "MAP", "kinase", "inhibitors", "as", "potential", "therapeutics", "for", "the", "treatment", "of", "joint", "degeneration", "and", "pain", "associated", "with", "osteoarthritis", "Kimberly", "K", "Brown,", "Sandra", "A", "Heitmeyer,", "Erin", "B", "Hookfin,", "Lily", "Hsieh,", "Maria", "Buchalova,", "Yetunde", "O", "Taiwo", "and", "Michael", "J", "Janusz*", "BioMed", "Central", "Open", "Access", "Address:", "Procter", "&", "Gamble", "Pharmaceuticals,", "Inc.", "8700", "Mason-Montgomery", "Rd.,", "Mason,", "OH", "45040-9462,", "USA", "Email:", "Kimberly", "K", "Brown", "-", "brown2kk@ucmail.uc.edu;", "Sandra", "A", "Heitmeyer", "-", "heitmeyer.sa@pg.com;", "Erin", "B", "Hookfin", "-", "hookfin.eb@pg.com;", "Lily", "Hsieh", "-", "peacelily2000@yahoo.com;", "Maria", "Buchalova", "-", "buchalova.m@pg.com;", "Yetunde", "O", "Taiwo", "-", "taiwoye@lilly.com;", "Michael", "J", "Janusz*", "-", "janusz.mj@pg.com", "*", "Corresponding", "author", "Published:", "4", "December", "2008", "Journal", "of", "Inflammation", "2008,", "5:22", "doi:10.1186/1476-9255-5-22", "This", "article", "is", "available", "from:", "http://www.journal-inflammation.com/content/5/1/22", "Received:", "12", "February", "2008", "Accepted:", "4", "December", "2008", "©", "2008", "Brown", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Evaluate", "the", "potential", "role", "of", "p38", "inhibitors", "for", "the", "treatment", "of", "osteoarthritis", "using", "an", "animal", "model", "of", "joint", "degeneration", "(iodoacetate-induced", "arthritis)", "and", "a", "pain", "model", "(Hargraeves", "assay).", "Methods:", "P38", "kinase", "activity", "was", "evaluated", "in", "a", "kinase", "assay", "by", "measuring", "the", "amount", "of", "phosphorylated", "substrate", "ATF2", "using", "a", "phosphoATF2", "(Thr71)", "specific", "primary", "antibody", "and", "an", "alkaline", "phosphate", "coupled", "secondary", "antibody", "and", "measuring", "the", "OD", "at", "405", "nm.", "TNFα", "and", "IL-1β", "secretion", "from", "LPS", "stimulated", "THP-1", "monocytic", "cells", "and", "human", "peripheral", "blood", "mononuclear", "cells", "were", "measured", "by", "ELISA.", "Rats", "treated", "with", "vehicle", "or", "p38", "inhibitor", "were", "injected", "intra-articularly", "in", "one", "knee", "with", "iodoacetate", "and", "damage", "to", "the", "tibial", "plateau", "was", "assessed", "from", "digitized", "images", "captured", "using", "an", "image", "analyzer.", "The", "effect", "of", "p38", "inhibitors", "on", "hyperalgesia", "was", "evaluated", "in", "rats", "given", "an", "intraplantar", "injection", "of", "carrageenan", "and", "4", "h", "later", "the", "paw", "withdrawal", "time", "to", "a", "radiant", "heat", "source", "was", "measured.", "Results:", "SB-203580", "and", "VX-745", "are", "both", "potent", "inhibitors", "of", "p38", "with", "IC50s", "of", "136", "±", "64", "nM", "and", "35", "±", "14", "nM", "(mean", "±", "S.D.),", "respectively.", "Similarly,", "SB-203580", "and", "VX-745", "potently", "inhibited", "TNF", "release", "from", "LPS", "stimulated", "human", "THP-1", "cells", "with", "IC50s", "of", "72", "±", "15", "nM;", "and", "29", "±", "14", "nM", "(mean", "±", "S.D.)", "respectively.", "TNF", "release", "from", "LPS", "stimulated", "human", "peripheral", "blood", "mononuclear", "cells", "was", "inhibited", "with", "IC50s", "16", "±", "6", "nM", "and", "14", "±", "8", "nM,", "(mean", "±", "S.D.)", "for", "SB-203580", "and", "VX-745", "and", "IL-1", "was", "inhibited", "with", "IC50s", "of", "20", "±", "8", "nM", "and", "15", "±", "4", "nM", "(mean", "±", "S.D.),", "respectively.", "SB-203580", "and", "VX-745", "administered", "orally", "at", "a", "dose", "of", "50", "mg/kg", "resulted", "in", "the", "significant", "(p", "<", "0.05)", "inhibition", "of", "joint", "degeneration", "in", "the", "rat", "iodoacetate", "model", "of", "45%", "and", "31%,", "respectively.", "SB-203580", "demonstrated", "a", "dose", "related", "inhibition", "of", "joint", "degeneration", "of", "30,", "25,", "12", "and", "8%", "at", "50,", "25,", "10", "and", "5", "mg/kg", "p.o.", "b.i.d.", "in", "the", "rat", "iodoacetate", "model.", "Similarly,", "both", "p38", "inhibitors", "significantly", "(p", "<", "0.05)", "attenuated", "the", "pain", "response", "(paw", "withdrawal", "time)", "in", "the", "Hargraeves", "hyperalgesia", "assay", "when", "administered", "orally", "at", "30,", "10", "and", "3", "mg/kg.", "Conclusion:", "SB203580", "and", "VX-745", "demonstrated", "attenuation", "of", "both", "cartilage", "degeneration", "and", "pain", "in", "animal", "models", "and", "suggest", "that", "p38", "inhibitors", "may", "be", "a", "useful", "approach", "for", "the", "treatment", "of", "osteoarthritis.", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Pita-Pereira", "et", "al.", "Parasites", "&", "Vectors", "2012,", "5:15", "http://www.parasitesandvectors.com/content/5/1/15", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "SYBR", "Green-based", "Real-Time", "PCR", "targeting", "kinetoplast", "DNA", "can", "be", "used", "to", "discriminate", "between", "the", "main", "etiologic", "agents", "of", "Brazilian", "cutaneous", "and", "visceral", "leishmaniases", "Daniela", "Pita-Pereira1,", "Rachel", "Lins2,", "Marcia", "P", "Oliveira3,", "Rosimar", "B", "Lima3,", "Bernardo", "AS", "Pereira1,", "Otacilio", "C", "Moreira1,", "Reginaldo", "P", "Brazil4", "and", "Constança", "Britto1*", "Abstract", "Background:", "Leishmaniases", "control", "has", "been", "hampered", "by", "the", "unavailability", "of", "rapid", "detection", "methods", "and", "the", "lack", "of", "suitable", "therapeutic", "and", "prophylactic", "measures.", "Accurate", "diagnosis,", "which", "can", "distinguish", "between", "Leishmania", "isolates,", "is", "essential", "for", "conducting", "appropriate", "prognosis,", "therapy", "and", "epidemiology.", "Molecular", "methods", "are", "currently", "being", "employed", "to", "detect", "Leishmania", "infection", "and", "categorize", "the", "parasites", "up", "to", "genus,", "complex", "or", "species", "level.", "Real-time", "PCR", "offers", "several", "advantages", "over", "traditional", "PCR,", "including", "faster", "processing", "time,", "higher", "sensitivity", "and", "decreased", "contamination", "risk.", "Results:", "A", "SYBR", "Green", "real-time", "PCR", "targeting", "the", "conserved", "region", "of", "kinetoplast", "DNA", "minicircles", "was", "able", "to", "differentiate", "between", "Leishmania", "subgenera.", "A", "panel", "of", "reference", "strains", "representing", "subgenera", "Leishmania", "and", "Viannia", "was", "evaluated", "by", "the", "derivative", "dissociation", "curve", "analyses", "of", "the", "amplified", "fragment.", "Distinct", "values", "for", "the", "average", "melting", "temperature", "were", "observed,", "being", "78.95°C", "±", "0.01", "and", "77.36°C", "±", "0.02", "for", "Leishmania", "and", "Viannia,", "respectively", "(p", "<", "0.05).", "Using", "the", "Neighbor-Joining", "method", "and", "Kimura", "2-parameters,", "the", "alignment", "of", "12", "sequences", "from", "the", "amplified", "conserved", "minicircles", "segment", "grouped", "together", "L.", "(V.)", "braziliensis", "and", "L.", "(V.)", "shawii", "with", "a", "bootstrap", "value", "of", "100%;", "while", "for", "L.", "(L.)", "infantum", "and", "L.", "(L.)", "amazonensis,", "two", "groups", "were", "formed", "with", "bootstrap", "values", "of", "100%", "and", "62%,", "respectively.", "The", "lower", "dissociation", "temperature", "observed", "for", "the", "subgenus", "Viannia", "amplicons", "could", "be", "due", "to", "a", "lower", "proportion", "of", "guanine/cytosine", "sites", "(43.6%)", "when", "compared", "to", "species", "from", "subgenus", "Leishmania", "(average", "of", "48.4%).", "The", "method", "was", "validated", "with", "30", "clinical", "specimens", "from", "visceral", "or", "cutaneous", "leishmaniases", "patients", "living", "in", "Brazil", "and", "also", "with", "DNA", "samples", "from", "naturally", "infected", "Lutzomyia", "spp.", "captured", "in", "two", "Brazilian", "localities.", "Conclusions:", "For", "all", "tested", "samples,", "a", "characteristic", "amplicon", "melting", "profile", "was", "evidenced", "for", "each", "Leishmania", "subgenus,", "corroborating", "the", "data", "from", "reference", "strains.", "Therefore,", "the", "analysis", "of", "thermal", "dissociation", "curves", "targeting", "the", "conserved", "kinetoplast", "DNA", "minicircles", "region", "is", "able", "to", "provide", "a", "rapid", "and", "reliable", "method", "to", "identify", "the", "main", "etiologic", "agents", "of", "cutaneous", "and", "visceral", "leishmaniases", "in", "endemic", "regions", "of", "Brazil.", "Keywords:", "SYBR", "Green", "Real-time", "PCR,", "Leishmaniases,", "kinetoplast", "DNA,", "thermal", "dissociation", "curves,", "molecular", "diag-", "nosis,", "Brazil", "*", "Correspondence:", "cbritto@ioc.fiocruz.br", "1Laboratório", "de", "Biologia", "Molecular", "e", "Doenças", "Endêmicas,", "Instituto", "Oswaldo", "Cruz,", "FIOCRUZ,", "Pavilhão", "Leônidas", "Deane,", "sala", "209,", "Avenida", "Brasil", "4365,", "Manguinhos,", "21040-360", "Rio", "de", "Janeiro,", "RJ,", "Brazil", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2012", "Pita-Pereira", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hamama", "et", "al.", "Fibrogenesis", "&", "Tissue", "Repair", "2012,", "5(Suppl", "1):S13", "http://www.fibrogenesis.com/content/5/S1/S13", "P", "R", "O", "C", "E", "E", "D", "I", "N", "G", "S", "Open", "Access", "Therapeutic", "management", "of", "intestinal", "fibrosis", "induced", "by", "radiation", "therapy:", "from", "molecular", "profiling", "to", "new", "intervention", "strategies", "et", "vice", "et", "versa", "Saad", "Hamama1,2,", "Sylvie", "Delanian1,2,3,", "Virginie", "Monceau1,", "Marie-Catherine", "Vozenin1,2*", "From", "Fibroproliferative", "disorders:", "from", "biochemical", "analysis", "to", "targeted", "therapies", "Frauenchiemsee,", "Germany.", "25-30", "September", "2010", "Abstract", "Chronic", "toxicities", "of", "locoregional", "and", "systemic", "oncological", "treatments", "commonly", "develop", "in", "long-term", "cancer", "survivors.", "Amongst", "these", "toxicities,", "post-radiotherapeutic", "complications", "alter", "patient’s", "quality", "of", "life.", "Reduction", "of", "exposure", "of", "normal", "tissues", "can", "be", "achieved", "by", "optimization", "of", "radiotherapy.", "Furthermore,", "understanding", "of", "the", "fibrogenic", "mechanisms", "has", "provided", "targets", "to", "prevent,", "mitigate,", "and", "reverse", "late", "radiation-induced", "damages.", "This", "mini-review", "shows", "how", "(i)", "global", "molecular", "studies", "using", "gene", "profiling", "can", "provide", "tools", "to", "develop", "new", "intervention", "strategies", "and", "(ii)", "how", "successful", "clinical", "trials,", "conducted", "in", "particular", "with", "combined", "pentoxifylline-", "vitamin", "E,", "can", "take", "benefice", "of", "biological", "and", "molecular", "evidences", "to", "improve", "our", "understanding", "of", "fibrogenic", "mechanisms,", "enhance", "the", "robustness", "of", "proposed", "treatments,", "and", "lead", "ultimately", "to", "better", "treatments", "for", "patient’s", "benefice.", "Introduction", "Therapeutic", "management", "of", "cancer", "improved", "during", "the", "past", "decade", "and", "is", "characterized", "today", "by", "a", "significant", "increase", "in", "patient’s", "survival", "rates.", "Although", "effective", "on", "cure", "rates,", "both", "locoregional", "and", "systemic", "oncological", "treatments", "present", "some", "concerns", "related", "to", "develop-", "ment", "of", "chronic", "toxicities", "that", "alter", "patient’s", "quality", "of", "life,", "while", "results", "of", "combined", "therapies", "suggest", "that", "normal", "tissue", "toxicity", "will", "become", "a", "major", "concern", "within", "the", "next", "years.", "Amongst", "these", "toxicities,", "radiation", "enteropathy", "is", "a", "significant", "delayed", "side", "effect", "of", "lumbar", "and", "pelvic", "radiotherapy.", "The", "risk,", "severity", "and", "nature", "of", "these", "radiation-induced", "toxicities", "depend", "on", "several", "factors", "including", "radiother-", "apy-related", "factors", "(total", "dose,", "dose", "per", "fraction", "and", "volume", "exposure)", "and", "patient-related", "factors", "(comorbid-", "ities)", "[1].", "Accordingly,", "a", "real", "effort", "has", "been", "made", "to", "*", "Correspondence:", "vozenin@igr.fr", "1INSERM", "U-1030", "“Molecular", "Radiotherapy”", "Institut", "Gustave", "Roussy,", "Villejuif,", "France", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "reduce", "normal", "tissue", "exposure", "by", "ballistic", "and", "imaging", "optimization", "of", "radiotherapy.", "Besides", "technological", "tools,", "understanding", "the", "fibrogenic", "mechanisms", "and", "targeting", "profibrotic", "factors", "has", "provided", "alternate", "and", "promising", "approaches", "to", "prevent,", "mitigate", "or", "even", "reverse", "late", "radia-", "tion-induced", "damages", "[1,2].", "If", "today’s", "clinical", "practice", "always", "aims", "to", "limit", "aggra-", "vating", "factors,", "current", "management", "of", "radiation-induced", "damages", "involves", "[3]:", "(i)", "anti-inflammatory", "treatments", "including", "corticosteroids;", "(ii)", "vascular", "therapy", "including", "pentoxifylline", "(PTX)", "or", "hyperbaric", "oxygen;", "(iii)", "antioxi-", "dant", "treatment", "including", "superoxide", "dismutase", "in", "the", "nineties", "and", "then", "combined", "pentoxifylline-vitamin", "E", "(PTX-VitE)", "in", "the", "last", "decade.", "The", "first", "part", "of", "this", "mini-review", "shows", "how", "global", "molecular", "studies", "using", "gene", "profiling", "can", "provide", "tools", "to", "develop", "new", "intervention", "strategies", "with", "old", "molecules", "or", "new", "compounds.", "The", "second", "part", "shows", "how", "successful", "clinical", "research", "done", "with", "well-known", "but", "low", "potent", "old", "drugs", "takes", "benefice", "of", "biological", "and", "molecular", "evidences", "to", "improve", "its", "robustness", "for", "patient’s", "benefice.", "©", "2012", "Hamama", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Gut", "and", "Liver,", "Vol.", "5,", "No.", "4,", "December", "2011,", "pp.", "539-542", "case", "report", "Stapled", "Mucosectomy:", "An", "Alternative", "Technique", "for", "the", "Removal", "of", "Retained", "Rectal", "Mucosa", "after", "Ileal", "Pouch-Anal", "Anastomosis", "Metin", "Ertem", "and", "Volkan", "Ozben", "Department", "of", "General", "Surgery,", "Cerrahpasa", "Medical", "School,", "Istanbul", "University,", "Istanbul,", "Turkey", "Restorative", "proctocolectomy", "(RPC),", "when", "performed", "with", "a", "stapled", "ileal", "pouch-anal", "anastomosis", "(IPAA),", "allows", "the", "retention", "of", "the", "rectal", "mucosa", "above", "the", "dentate", "line", "and", "can", "result", "in", "disease", "persistence", "or", "recurrence,", "as", "well", "as", "neoplastic", "lesions", "in", "patients", "with", "ulcerative", "colitis", "(UC).", "We", "report", "the", "case", "of", "a", "patient", "with", "chronic", "UC", "who", "underwent", "staple", "mucosectomy,", "which", "is", "an", "alternative", "technique", "that", "evolved", "from", "stapled", "hemorrhoidopexy,", "rather", "than", "more", "traditional", "procedures.", "The", "patient", "had", "undergone", "laparo-", "scopic", "RPC", "with", "a", "stapled", "IPAA", "2", "cm", "above", "the", "dentate", "line", "and", "a", "temporary", "loop", "ileostomy.", "Because", "the", "histopathology", "showed", "low-grade", "dysplasia", "in", "the", "proximal", "rectum,", "stapled", "mucosectomy", "with", "a", "33-mm", "circular", "stapler", "kit", "at", "the", "time", "of", "ileostomy", "closure", "was", "scheduled.", "Following", "the", "application", "of", "a", "purse-string", "suture", "1", "cm", "above", "the", "dentate", "line,", "the", "sta-", "pler", "was", "inserted", "with", "its", "anvil", "beyond", "the", "purse-string", "and", "was", "fired.", "The", "excised", "rectal", "tissue", "was", "checked", "to", "ensure", "that", "it", "was", "a", "complete", "cylindrical", "doughnut.", "Histopathology", "of", "the", "excised", "tissue", "showed", "chronic", "inflammation.", "There", "were", "no", "complications", "during", "a", "follow-up", "period", "of", "5", "months.", "Because", "it", "preserves", "the", "normal", "rectal", "mucosal", "architecture", "and", "avoids", "a", "complex", "mucosectomy", "surgery,", "stapled", "muco-", "sectomy", "seems", "to", "be", "a", "technically", "feasible", "and", "clinically", "ac-", "ceptable", "alternative", "to", "the", "removal", "of", "rectal", "mucosa", "retained", "after", "RPC.", "(Gut", "Liver", "2011;5:539-542)", "Key", "Words:", "Ulcerative", "colitis;", "Retained", "rectal", "mucosa;", "Sta-", "pled", "mucosectomy;", "Surgical", "technique", "INTRODUCTION", "Restorative", "proctocolectomy", "(RPC)", "with", "ileal", "pouch-anal", "anastomosis", "(IPAA)", "is", "now", "considered", "the", "procedure", "of", "choice", "for", "the", "surgical", "treatment", "of", "patients", "with", "ulcerative", "colitis", "(UC).1-3", "The", "IPAA", "can", "be", "performed", "using", "either", "a", "stapling", "tech-", "nique", "or", "a", "handsewn", "technique", "with", "mucosectomy.", "Currently,", "double", "stapled", "IPAA", "is", "favoured", "as", "it", "is", "simpler", "and", "provides", "better", "functional", "results", "than", "the", "handsewn", "IPAA", "with", "muco-", "sectomy.1,3", "On", "the", "other", "hand,", "the", "stapled", "technique", "allows", "the", "retention", "of", "1", "to", "2", "cm", "strip", "of", "the", "rectal", "and", "anal", "transition", "zone", "mucosa", "above", "the", "dentate", "line.", "Since", "UC", "is", "a", "mucosal", "disease,", "often", "originating", "in", "the", "rectum", "and", "progressing", "proximally,", "retention", "of", "the", "potentially", "diseased", "rectal", "mucosa", "exposes", "UC", "patients", "not", "only", "to", "chronic", "inflam-", "mation", "or", "disease", "recurrence", "but", "also", "to", "neoplastic", "lesions,", "as", "already", "reported.2,4", "For", "this", "reason,", "a", "number", "of", "techniques", "have", "been", "proposed", "in", "order", "to", "eradicate", "the", "rectal", "mucosa,5-10", "how-", "ever,", "these", "techniques", "harbor", "several", "disadvantages", "with", "respect", "to", "either", "technical", "aspects", "or", "histopathologic", "interpretation", "of", "the", "excised", "tissue.", "Here,", "we", "report", "on", "a", "case", "in", "order", "to", "intro-", "duce", "an", "alternative", "technique,", "stapled", "mucosectomy,", "for", "the", "removal", "of", "the", "rectal", "mucosa", "retained", "after", "previous", "RPC", "with", "stapled", "IPAA.", "CASE", "REPORT", "A", "62-year-old", "male", "patient", "who", "had", "had", "a", "7-year", "history", "of", "UC", "refractory", "to", "medical", "therapy", "underwent", "laparoscopic", "RPC", "with", "an", "ileal", "J-pouch,", "IPAA", "and", "temporary", "loop", "ileostomy", "in", "our", "institution.", "The", "J-pouch", "was", "created", "with", "the", "stapled", "tech-", "nique", "and", "the", "pouch", "was", "anastomozed", "approximately", "2", "cm", "above", "the", "dentate", "line", "using", "a", "31-mm", "transanal", "circular", "stapler.", "Postoperatively,", "the", "patient", "was", "discharged", "home", "after", "an", "un-", "eventful", "recovery.", "The", "histopathology", "of", "the", "proctocolectomy", "specimen", "showed", "low", "grade", "dysplasia", "in", "the", "proximal", "rectum", "with", "no", "evidence", "of", "malignancy", "throughout", "the", "colon.", "Based", "on", "the", "result", "of", "the", "histolopathology,", "an", "elective", "surgery", "for", "a", "completion", "mucosectomy", "at", "the", "time", "of", "ileostomy", "closure", "was", "Correspondence", "to:", "Volkan", "Ozben", "Department", "of", "General", "Surgery,", "Cerrahpasa", "Medical", "School,", "Istanbul", "University,", "Surmene", "Devlet", "Hastanesi,", "Genel", "Cerrahi", "Klinigi,", "P.O.", "Box:", "61600,", "Surmene,", "Trabzon,", "Turkey", "Tel:", "+90-462-746-1422,", "Fax:", "+90-462-746-1429,", "E-mail:", "volkanozben@yahoo.co.uk", "Received", "on", "June", "17,", "2010.", "Accepted", "on", "August", "2,", "2010.", "pISSN", "1976-2283", "eISSN", "2005-1212", "http://dx.doi.org/10.5009/gnl.2011.5.4.539", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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"biological", "imaging;", "(170.3890)", "Medical", "optics", "instrumentation;", "(230.4685)", "Optical", "microelectromechanical", "devices", "References", "and", "links", "1.", "M.", "Rajadhyaksha,", "S.", "González,", "J.", "M.", "Zavislan,", "R.", "R.", "Anderson,", "and", "R.", "H.", "Webb,", "“In", "vivo", "confocal", "scanning", "laser", "microscopy", "of", "human", "skin", "II:", "advances", "in", "instrumentation", "and", "comparison", "with", "histology,”", "J.", "Invest.", "Dermatol.", "113(3),", "293–303", "(1999).", "2.", "K.", "S.", "Nehal,", "D.", "Gareau,", "and", "M.", "Rajadhyaksha,", "“Skin", "imaging", "with", "reflectance", "confocal", "microscopy,”", "Semin.", "Cutan.", "Med.", "Surg.", "27(1),", "37–43", "(2008).", "3.", "P.", "Corcuff,", "and", "J.", "L.", "Lévêque,", "“In", "vivo", "vision", "of", "the", "human", "skin", "with", "the", "tandem", "scanning", "microscope,”", "Dermatology", "186(1),", "50–54", "(1993).", "4.", "G.", "Pellacani,", "A.", "M.", 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[ "Molecular", "Pain", "Methodology", "Detection", "of", "cold", "pain,", "cold", "allodynia", "and", "cold", "hyperalgesia", "in", "freely", "behaving", "rats", "Andrew", "J", "Allchorne†1,", "Daniel", "C", "Broom†1,2", "and", "Clifford", "J", "Woolf*1", "BioMed", "Central", "Open", "Access", "Address:", "1Neural", "Plasticity", "Research", "Group,", "Department", "of", "Anesthesia", "&", "Critical", "Care,", "Massachusetts", "General", "Hospital", "&", "Harvard", "Medical", "School,", "13th", "Street,", "Building", "149", "(#4309),", "Charlestown,", "MA", "02129,", "USA", "and", "2Neurogen", "Corporation,", "35", "NE", "Industrial", "Rd.,", "Branford,", "CT", "06405,", "USA", "Email:", "Andrew", "J", "Allchorne", "-", "andrew.allchorne@gmail.com;", "Daniel", "C", "Broom", "-", "dbroom@nrgn.com;", "Clifford", "J", "Woolf*", "-", "cwoolf@partners.org", "*", "Corresponding", "author", "†Equal", "contributors", "Published:", "14", "December", "2005", "Molecular", "Pain", "2005,", "1:36", "doi:10.1186/1744-8069-1-36", "This", "article", "is", "available", "from:", "http://www.molecularpain.com/content/1/1/36", "Received:", "25", "November", "2005", "Accepted:", "14", "December", "2005", "©", "2005", "Allchorne", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Pain", "is", "elicited", "by", "cold,", "and", "a", "major", "feature", "of", "many", "neuropathic", "pain", "states", "is", "that", "normally", "innocuous", "cool", "stimuli", "begin", "to", "produce", "pain", "(cold", "allodynia).", "To", "expand", "our", "understanding", "of", "cold", "induced", "pain", "states", "we", "have", "studied", "cold", "pain", "behaviors", "over", "a", "range", "of", "temperatures", "in", "several", "animal", "models", "of", "chronic", "pain.", "Results:", "We", "demonstrate", "that", "a", "Peltier-cooled", "cold", "plate", "with", "±", "1°C", "sensitivity", "enables", "quantitative", "measurement", "of", "a", "detection", "withdrawal", "response", "to", "cold", "stimuli", "in", "unrestrained", "rats.", "In", "naïve", "rats", "the", "threshold", "for", "eliciting", "cold", "pain", "behavior", "is", "5°C.", "The", "withdrawal", "threshold", "for", "cold", "allodynia", "is", "15°C", "in", "both", "the", "spared", "nerve", "injury", "and", "spinal", "nerve", "ligation", "models", "of", "neuropathic", "pain.", "Cold", "hyperalgesia", "is", "present", "in", "the", "spared", "nerve", "injury", "model", "animals,", "manifesting", "as", "a", "reduced", "latency", "of", "withdrawal", "response", "threshold", "at", "temperatures", "that", "elicit", "cold", "pain", "in", "naïve", "rats.", "We", "also", "show", "that", "following", "the", "peripheral", "inflammation", "produced", "by", "intraplantar", "injection", "of", "complete", "Freund's", "adjuvant,", "a", "hypersensitivity", "to", "cold", "occurs.", "Conclusion:", "The", "peltier-cooled", "provides", "an", "effective", "means", "of", "assaying", "cold", "sensitivity", "in", "unrestrained", "rats.", "Behavioral", "testing", "of", "cold", "allodynia,", "hyperalgesia", "and", "pain", "will", "greatly", "facilitate", "the", "study", "of", "the", "neurobiological", "mechanisms", "involved", "in", "cold/cool", "sensations", "and", "enable", "measurement", "of", "the", "efficacy", "of", "pharmacological", "treatments", "to", "reduce", "these", "symptoms.", "Background", "Neuropathic", "pain", "patients", "exhibit", "a", "wide", "range", "of", "symp-", "toms", "including", "spontaneous", "and", "stimulus-evoked", "pain", "[1].", "The", "latter", "include", "tactile", "allodynia", "(pain", "caused", "by", "a", "normally", "innocuous", "stimulus),", "pinprick", "hyperalgesia", "(heightened", "sensitivity", "to", "a", "painful", "stimulus),", "altered", "sen-", "sitivity", "to", "heat,", "cold", "hyperalgesia", "(heightened", "sensitivity", "to", "a", "painful", "cold", "stimulus)", "and", "cold", "allodynia", "(pain", "caused", "by", "a", "normally", "innocuous", "cold", "stimulus).", "Cold", "hyperalgesia", "is", "present", "in", "9%", "of", "patients", "with", "varying", "neu-", "ropathies", "[2]", "and", "23%", "of", "patients", "with", "post", "stroke", "central", "pain", "(CPSP)", "exhibited", "cold", "allodynia", "[3].", "Many", "rodent", "models", "of", "neuropathic", "pain", "have", "been", "developed", "and", "characterized", "using", "standardized", "limb", "withdrawal", "meas-", "ures", "as", "a", "surrogate", "for", "the", "sensory", "threshold", "or", "responsive-", "ness", "to", "innocuous", "or", "noxious", "stimuli,", "such", "as;", "von", "Frey", "hairs", "and", "sensitivity", "to", "brush", "for", "mechanical", "allodynia,", "pin", "prick", "for", "mechanical", "hyperalgesia,", "hot", "plate", "and", "radi-", "ant", "heat", "for", "heat", "pain.", "A", "number", "of", "techniques", "have", "been", "employed", "for", "studying", "cold", "pain", "and", "cold", "allodynia", "using", "reflex", "responses", "(lifting", "of", "the", "hindpaw)", "or", "behavioral", "escape", "endpoints.", "These", "methods", "include:", "The", "applica-", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "CLINICS", "2012;67(5):525-526", "CASE", "REPORT", "DOI:10.6061/clinics/2012(05)21", "Early", "diagnosis", "of", "acute", "kidney", "injury", "in", "a", "critically", "ill", "patient", "using", "a", "combination", "of", "blood", "and", "urinary", "physicochemical", "parameters", "Alexandre", "Toledo", "Maciel,", "Marcelo", "Park", "Instituto", "Central", "do", "Hospital", "das", "Clı´nicas", "da", "Faculdade", "de", "Medicina", "da", "Universidade", "de", "Sa˜", "o", "Paulo,", "Intensive", "Care", "Unit,", "Department", "of", "Medical", "Emergencies,", "S", "a˜o", "Paulo,SP/Brazil.", "Email:", "toledomaciel2003@yahoo.com.br", "Tel.:", "55", "11", "9343-0960", "INTRODUCTION", "Acute", "kidney", "injury", "(AKI)", "is", "common", "among", "critically", "ill", "patients.", "Because", "it", "is", "associated", "with", "high", "rates", "of", "morbidity", "and", "mortality,", "efforts", "are", "being", "made", "to", "identify", "AKI", "early", "to", "increase", "the", "likelihood", "of", "successful", "interven-", "tion.", "Serum", "creatinine,", "the", "primary", "parameter", "used", "to", "diagnose", "AKI,", "is", "universally", "considered", "a", "late", "marker.", "One", "of", "the", "major", "problems", "associated", "with", "AKI", "is", "acid-", "base", "disturbance.", "The", "physicochemical", "approach", "proposed", "by", "Stewart", "(1)", "is", "increasingly", "recognized", "as", "useful", "in", "managing", "complex", "acid-base", "disturbances.", "In", "this", "case,", "we", "demonstrate", "that,", "during", "the", "development", "of", "AKI,", "evolutive", "alterations", "in", "physicochemical", "serum", "and", "urinary", "variables", "are", "easily", "measured", "and", "may", "reliably", "precede", "increases", "in", "creatinine.", "These", "parameters", "may", "thus", "aid", "in", "the", "early", "diagnosis", "of", "AKI.", "CASE", "DESCRIPTION", "A", "45-year-old", "male", "was", "admitted", "to", "our", "intensive", "care", "unit", "(ICU)", "from", "the", "ward,", "where", "he", "was", "concluding", "antibiotic", "treatment", "for", "a", "urinary", "tract", "infection", "and", "being", "treated", "with", "oral", "anticoagulants", "for", "antiphospholipid", "syndrome.", "On", "the", "day", "of", "ICU", "admission", "(day", "0),", "the", "patient", "was", "found", "unconscious", "on", "the", "floor", "of", "the", "ward.", "A", "cranial", "CT", "scan", "revealed", "an", "acute", "subdural", "hematoma.", "The", "patient", "was", "immediately", "transferred", "to", "the", "ICU", "and", "intubated.", "The", "anticoagulant", "was", "reversed", "with", "vitamin", "K", "and", "plasma.", "Soon", "after,", "the", "patient", "was", "transferred", "to", "the", "operating", "room,", "where", "the", "hematoma", "was", "drained", "and", "an", "intracranial", "pressure", "(ICP)", "monitoring", "device", "was", "installed.", "After", "the", "surgery,", "the", "patient", "returned", "to", "the", "ICU.", "Because", "of", "his", "elevated", "ICP,", "the", "patient", "was", "kept", "sedated", "with", "thiopental.", "Norepinephrine", "was", "infused", "to", "maintain", "an", "adequate", "cerebral-perfusion", "pressure.", "Initial", "exams", "after", "surgery", "(day", "1)", "revealed", "normal", "blood", "urea", "nitrogen", "(BUN)", "and", "creatinine", "levels", "and", "increased", "levels", "of", "serum", "Na+", "and", "Cl-", "(Table", "1).", "Blood", "gas", "analysis", "revealed", "a", "mild", "non-anion", "gap", "metabolic", "acidosis.", "A", "simultaneous", "spot", "sample", "of", "urine", "also", "revealed", "Copyright", "2012", "CLINICS", "–", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://", "creativecommons.org/licenses/by-nc/3.0/)", "which", "permits", "unrestricted", "non-", "commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "No", "potential", "conflict", "of", "interest", "was", "reported.", "525", "high", "levels", "of", "Na+", "(NaU)", "and", "Cl-", "(ClU)", "as", "well", "as", "a", "high", "urinary", "strong", "ion", "difference", "(SIDu", "=", "[Na+]+[K+]–[Cl-]).", "By", "day", "2,", "BUN", "and", "creatinine", "levels", "had", "decreased", "slightly.", "Urine", "output", "over", "the", "previous", "24", "h", "had", "been", "normal.", "Serum", "and", "urine", "levels", "of", "Na+", "and", "Cl-", "remained", "elevated,", "and", "the", "SIDu", "remained", "high,", "but", "the", "blood", "gas", "analysis", "was", "normal.", "The", "ICP", "was", "controlled;", "thiopental", "was", "replaced", "by", "dexme-", "detomidine,", "and", "the", "dose", "of", "norepinephrine", "was", "reduced.", "By", "day", "3,", "BUN", "and", "creatinine", "levels", "had", "increased", "only", "minimally.", "Urine", "output", "had", "decreased", "over", "the", "previous", "24", "h", "but", "did", "not", "fall", "below", "the", "normal", "range", "(Table", "1).", "Serum", "Na+", "and", "Cl-", "levels", "were", "evolutively", "similar,", "while", "NaU", "and", "ClU", "levels", "remained", "high.", "A", "significant", "increase", "in", "SIDu", "was", "observed,", "which", "resulted", "from", "increases", "in", "NaU", "and", "K+", "(KU)", "levels", "and", "decreases", "in", "ClU", "levels", "(Figure", "1).", "Sedation", "was", "stopped,", "but", "norepinephrine", "was", "still", "necessary", "to", "maintain", "the", "patient’s", "mean", "blood", "pressure", "above", "65", "mmHg.", "C-", "reactive", "protein", "levels", "and", "the", "degree", "of", "leukocytosis", "increased", "daily,", "and", "cultures", "were", "collected.", "On", "day", "4,", "the", "patient", "developed", "tachycardia,", "and", "urinary", "flow", "continued", "to", "decrease,", "while", "norepinephrine", "levels", "increased", "to", "maintain", "the", "mean", "blood", "pressure.", "There", "was", "no", "fever.", "Treatment", "with", "broad-spectrum", "antibiotics", "was", "initiated", "empirically.", "During", "this", "time,", "creatinine", "levels", "had", "not", "increased,", "but", "the", "BUN", "level", "increased", "slowly", "each", "day", "to", "levels", "that", "did", "not", "exceed", "the", "normal", "range.", "Serum", "phosphate", "and", "unmeasured", "anions", "(Table", "1)", "also", "increased", "daily.", "Serum", "Na+", "and", "Cl-", "were", "still", "high,", "but", "NaU", "and", "ClU", "levels", "decreased;", "KU", "levels", "increased", "daily", "from", "day", "2", "onward.", "On", "day", "5,", "the", "patient", "developed", "clear", "oliguria,", "although", "the", "creatinine", "measurements", "per-", "formed", "at", "the", "beginning", "of", "the", "day", "were", "normal.", "The", "BUN", "level", "continued", "to", "increase.", "An", "abrupt", "decrease", "in", "NaU", "and", "ClU", "levels", "occurred", "in", "parallel", "with", "the", "increases", "in", "KU", "levels.", "The", "SIDu", "decreased", "but", "remained", "very", "high.", "On", "day", "6,", "the", "patient", "developed", "fever,", "severe", "metabolic", "acidosis,", "and", "refractory", "shock", "with", "overt", "multiple-organ", "failure.", "NaU", "and", "ClU", "levels", "fell", "further,", "but", "the", "KU", "and", "SIDu", "levels", "remained", "high.", "The", "patient’s", "creatinine", "levels", "increased", "abruptly,", "and", "the", "nephrology", "team", "indicated", "the", "need", "for", "continuous", "renal-", "replacement", "therapy;", "however,", "the", "patient", "died", "before", "therapy", "could", "be", "initiated.", "None", "of", "the", "cultures", "collected", "revealed", "the", "presence", "of", "an", "infectious", "agent.", "DISCUSSION", "The", "case", "described", "above", "is", "a", "common", "example", "of", "AKI", "(possibly", "septic", "in", "origin),", "and", "it", "demonstrates", "that", "creatinine" ]

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[ "MINI", "REVIEW", "ARTICLE", "published:", "23", "April", "2012", "doi:", "10.3389/fpls.2012.00074", "Transcriptional", "regulation", "of", "grass", "secondary", "cell", "wall", "biosynthesis:", "playing", "catch-up", "with", "Arabidopsis", "thaliana", "Pubudu", "P.", "Handakumbura1,2", "and", "Samuel", "P.", "Hazen1*", "1", "Biology", "Department,", "University", "of", "Massachusetts,", "Amherst,", "MA,", "USA", "2", "Plant", "Biology", "Graduate", "Program,", "University", "of", "Massachusetts,", "Amherst,", "MA,", "USA", "Edited", "by:", "Jose", "Manuel", "Estevez,", "University", "of", "Buenos", "Aires", "and", "CONICET,", "Argentina", "Reviewed", "by:", "Uener", "Kolukisaoglu,", "University", "of", "Tuebingen,", "Germany", "Vasileios", "Fotopoulos,", "Cyprus", "University", "of", "Technology,", "Cyprus", "*Correspondence:", "Samuel", "P.", "Hazen,", "Biology", "Department,", "University", "of", "Massachusetts,", "221", "Morrill", "Science", "Center,", "Amherst,", "MA", "01003,", "USA.", "e-mail:", "hazen@bio.umass.edu", "Secondary", "cell", "wall", "synthesis", "occurs", "in", "specialized", "cell", "types", "following", "completion", "of", "cell", "enlargement.", "By", "virtue", "of", "mechanical", "strength", "provided", "by", "a", "wall", "thickened", "with", "cellu-", "lose,", "hemicelluloses,", "and", "lignin,", "these", "cells", "can", "function", "as", "water-conducting", "vessels", "and", "provide", "structural", "support.", "Several", "transcription", "factor", "families", "regulate", "genes", "encoding", "wall", "synthesis", "enzymes.", "Certain", "NAC", "and", "MYB", "proteins", "directly", "bind", "to", "the", "SNBE", "and", "AC", "elements", "upstream", "of", "structural", "genes", "and", "other", "transcription", "factors.", "The", "most", "detailed", "model", "of", "this", "regulatory", "network", "is", "established", "predominantly", "for", "a", "eudicot,", "Arabidop-", "sis", "thaliana.", "In", "grasses,", "both", "the", "patterning", "and", "the", "composition", "of", "secondary", "cell", "walls", "are", "distinct", "from", "that", "of", "eudicots.", "These", "differences", "suggest", "transcriptional", "regulation", "is", "similarly", "distinct.", "Putative", "rice", "and", "maize", "orthologs", "of", "several", "eudicot", "cell", "wall", "regulators", "genetically", "complement", "mutants", "of", "A.", "thaliana", "or", "result", "in", "wall", "defects", "when", "constitutively", "overexpressed;", "nevertheless,", "aside", "from", "a", "maize,", "ZmMYB31,", "and", "a", "switchgrass", "protein,", "PvMYB4,", "function", "has", "not", "been", "tested", "in", "a", "grass.", "Similar", "to", "the", "seminal", "work", "conducted", "in", "A.", "thaliana,", "gene", "expression", "profiling", "in", "maize,", "rice,", "and", "other", "grasses", "implicates", "addi-", "tional", "genes", "as", "regulators.", "Characterization", "of", "these", "genes", "will", "continue", "to", "elucidate", "the", "relationship", "between", "the", "transcription", "regulatory", "networks", "of", "eudicots", "and", "grasses.", "Keywords:", "transcription", "factors,", "secondary", "cell", "wall", "INTRODUCTION", "Plant", "cell", "walls", "are", "diverse", "in", "their", "polymer", "composition,", "which", "vary", "among", "plant", "species", "as", "well", "as", "cell", "types", "within", "a", "species.", "The", "primary", "cell", "wall,", "consisting", "mostly", "of", "cellulose,", "hemicelluloses,", "pectin,", "and", "proteins", "demarcates", "each", "plant", "cell.", "Secondary", "cell", "walls,", "composed", "mostly", "of", "cellulose,", "hemicelluloses,", "and", "lignin,", "are", "deposited", "between", "the", "plasma", "membrane", "and", "primary", "wall", "in", "specialized", "cell", "types", "following", "cessation", "of", "cell", "enlargement.", "Even", "though", "all", "plant", "cell", "walls", "contain", "a", "cell", "wall", "matrix", "made", "up", "of", "cellulose", "microfibrils,", "hemicelluloses,", "and", "other", "cell", "wall", "poly-", "mers,", "there", "are", "significant", "differences", "in", "polymer", "types", "and", "their", "relative", "abundance", "between", "dictos", "and", "monocots", "(Vogel,", "2008).", "For", "instance,", "relatively", "high", "amounts", "of", "xyloglucan,", "pectins,", "and", "structural", "proteins", "are", "typically", "present", "in", "the", "primary", "walls", "of", "eudicots,", "non-commelinoid", "monocots,", "and", "gymnosperms.", "The", "commelinoid", "monocots", "like", "grasses", "contain", "glucuronoarabinoxy-", "lans,", "small", "quantities", "of", "pectin", "and", "structural", "proteins", "and", "high", "levels", "of", "hydroxycinnamates", "(Vogel,", "2008).", "Apart", "from", "wall", "com-", "position,", "eudicots", "such", "as", "Arabidopsis", "thaliana", "and", "monocots", "such", "as", "rice", "(Oryza", "sativa", "L.)", "exhibit", "distinct", "morphological", "character-", "istics", "in", "addition", "to", "their", "namesake", "two", "and", "single", "cotyledons.", "Pinnate", "or", "palmate", "venation", "is", "characteristic", "of", "eudicots", "while", "monocots", "posses", "parallel", "venation.", "Other", "morphological", "and", "anatomical", "distinctions", "exist", "in", "their", "vasculature,", "tissues", "highly", "enriched", "in", "secondary", "cell", "walls.", "Stem", "radial", "thickening", "in", "eudi-", "cots", "is", "derived", "from", "a", "specialized", "cell", "layer", "called", "the", "cambium", "that", "differentiates", "into", "the", "phloem", "and", "xylem.", "On", "the", "other", "hand,", "monocots", "lack", "a", "specialized", "cambium", "layer", "and", "therefore", "do", "not", "undergo", "secondary", "growth", "(Figure", "1).", "The", "vascular", "bundles", "of", "grasses", "are", "often", "well", "defined", "by", "a", "single", "layer", "of", "bundle", "sheath", "cells", "surrounding", "the", "xylem", "and", "phloem", "and", "the", "organization", "of", "the", "bundles", "is", "distinct", "from", "eudicots.", "In", "A.", "thaliana,", "the", "vascular", "bundles", "are", "arranged", "as", "a", "ring", "along", "the", "periphery", "of", "the", "stem", "in", "a", "pattern", "known", "as", "eustelic,", "whereas", "monocot", "bundles", "posses", "an", "atactostele", "arrangement", "characterized", "by", "several", "circles", "around", "the", "periphery", "of", "a", "stem,", "as", "in", "rice", "and", "Brachypodium", "distachyon", "(Figure", "1),", "or", "scattered", "throughout", "the", "stem", "as", "in", "maize", "(Zea", "mays", "L.;", "Kiesselbach,", "1949).", "With", "distinctions", "and", "similarities", "abound,", "it", "is", "decidedly", "unclear", "how", "the", "transcriptional", "regulation", "of", "secondary", "cell", "wall", "biosynthesis", "in", "eudicots", "and", "grasses", "relate.", "Plant", "cell", "wall", "biosyn-", "thesis", "is", "regulated", "at", "different", "molecular", "and", "cellular", "levels.", "Current", "evidence", "supports", "a", "complex", "regulatory", "network", "consisting", "of", "a", "handful", "of", "proteins", "from", "only", "a", "small", "portion", "of", "over", "65", "different", "transcription", "factor", "families", "(Figure", "2A).", "Phylogenetic", "analysis", "has", "identified", "close", "homologs", "of", "A.", "thaliana", "regulators", "from", "both", "vas-", "cular", "and", "non-vascular", "plants", "and", "some", "of", "those", "regulators", "were", "capable", "of", "complementing", "A.", "thaliana", "cell", "wall", "mutants", "(Zhong", "et", "al.,", "2011).", "These", "findings", "suggest", "the", "evolutionary", "conservation", "of", "the", "transcriptional", "regulators", "in", "secondary", "cell", "wall", "biosynthe-", "sis.", "On", "the", "other", "hand,", "due", "to", "the", "pronounced", "differences", "between", "eudicot", "and", "monocot", "secondary", "wall", "composition", "and", "anatomy,", "there", "are", "likely", "unique", "aspects", "of", "the", "regulatory", "network", "yet", "to", "be", "resolved.", "www.frontiersin.org", "April", "2012", "|", "Volume", "3", "|", "Article", "74", "|", "1" ]

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[ "World", "J", "Microbiol", "Biotechnol", "(2011)", "27:805–811", "DOI", "10.1007/s11274-010-0520-6", "O", "R", "I", "G", "I", "N", "A", "L", "P", "A", "P", "E", "R", "Induction", "of", "aromatic", "ring:", "cleavage", "dioxygenases", "in", "Stenotrophomonas", "maltophilia", "strain", "KB2", "in", "cometabolic", "systems", "Danuta", "Wojcieszyn´", "ska", "•", "Urszula", "Guzik", "•", "Izabela", "Gren´", "•", "Magdalena", "Perkosz", "•", "Katarzyna", "Hupert-Kocurek", "Received:", "28", "May", "2010", "/", "Accepted:", "27", "July", "2010", "/", "Published", "online:", "10", "August", "2010", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Stenotrophomonas", "maltophilia", "KB2", "is", "known", "to", "produce", "different", "enzymes", "of", "dioxygenase", "family.", "The", "aim", "of", "our", "studies", "was", "to", "determine", "activity", "of", "these", "enzymes", "after", "induction", "by", "benzoic", "acids", "in", "cometabolic", "systems", "with", "nitrophenols.", "We", "have", "shown", "that", "under", "cometabolic", "con-", "ditions", "KB2", "strain", "degraded", "0.25–0.4", "mM", "of", "nitrophenols", "after", "14", "days", "of", "incubation.", "Simultaneously", "degradation", "of", "3", "mM", "of", "growth", "substrate", "during", "1–3", "days", "was", "observed", "depending", "on", "substrate", "as", "well", "as", "cometabolite", "used.", "From", "cometabolic", "systems", "with", "nitrophenols", "as", "cometabolites", "and", "3,4-dihydroxybenzoate", "as", "a", "growth", "substrate,", "dioxygenases", "with", "the", "highest", "activity", "of", "protocatechuate", "3,4-dioxygenase", "were", "isolated.", "Activity", "of", "catechol", "1,2-", "dioxygenase", "and", "protocatechuate", "4,5-dioxygenase", "was", "not", "observed.", "Cate-", "chol", "2,3-dioxygenase", "was", "active", "only", "in", "cultures", "with", "4-nitrophenol.", "Ability", "of", "KB2", "strain", "to", "induce", "and", "synthe-", "size", "various", "dioxygenases", "depending", "on", "substrate", "present", "in", "medium", "makes", "this", "strain", "useful", "in", "bioremediation", "of", "sites", "contaminated", "with", "different", "aromatic", "compounds.", "Nitrophenols", "Cometabolism", "Dioxygenase", "Keywords", "Induction", "Introduction", "Under", "aerobic", "conditions", "aromatic", "compounds,", "with", "the", "exception", "of", "those", "with", "deactivated", "substituent", "group,", "D.", "Wojcieszyn´ska", "U.", "Guzik", "(&)", "I.", "Gren´", "M.", "Perkosz", "K.", "Hupert-Kocurek", "Faculty", "of", "Biology", "and", "Environment", "Protection,", "Department", "of", "Biochemistry,", "University", "of", "Silesia,", "Jagiellonska", "28,", "40-032", "Katowice,", "Poland", "e-mail:", "urszula.guzik@us.edu.pl", "undergo", "degradation", "through", "oxygenetic", "ring", "fission", "by", "catechol", "1,2-", "or", "2,3-dioxygenase", "as", "well", "as", "protocatechuate", "3,4-", "or", "4,5-dioxygenase.", "Presence", "of", "deactivated", "substitu-", "ents", "with", "strong", "electrophilic", "properties", "makes", "the", "attack", "of", "oxygen", "on", "aromatic", "ring", "impossible", "(Pitter", "1985).", "Since", "the", "nitro", "group", "is", "a", "powerful", "deactivating", "substituent", "aerobic", "degradation", "of", "these", "substrates", "occurs", "generally", "through", "the", "reduction", "as", "well", "as", "regrouping", "and", "elimination", "of", "the", "nitrate", "group", "following", "aromatic", "ring", "cleavage", "(Blasco", "et", "al.", "1999;", "Schenzle", "et", "al.", "1997).", "Transformation", "of", "polynitrated", "aro-", "matic", "compounds", "by", "F420-dependent", "enzymatic", "complex", "and", "hydride", "d-complex", "formation", "was", "also", "shown", "(Ebert", "et", "al.", "1999).", "Some", "microorganisms", "degrade", "nitrophenols", "through", "aromatic", "ring", "fission", "by", "dioxygenases", "without", "prior", "removal", "of", "the", "nitrate", "group.", "However", "degradation", "of", "ni-", "trophenols", "occurs", "most", "often", "through", "their", "hydroxylation", "to", "benzenotriol,", "which", "is", "the", "ring", "fission", "substrate", "for", "hydro-", "quinone", "1,2-dioxygenase", "(Chauhan", "et", "al.", "2000;", "Pakala", "et", "al.", "2007),", "Walia", "et", "al.", "(2002)", "have", "shown", "activity", "of", "nitrocate-", "chol", "2,3-", "dioxygenase", "catalyzing", "transformation", "of", "4-nitro-", "catechol", "into", "3-nitro-2-hydroxy-6-oxo-hexa-2,4-dienoic", "acid", "in", "Pseudomonas", "putida", "strain.", "In", "other", "study", "Kieboom", "et", "al.", "(2001)", "have", "observed", "induction", "of", "2,3-", "dioxygenase", "in", "Nocardia", "strain", "S3", "in", "the", "presence", "of", "3-nitrocatechol.", "It", "has", "been", "shown", "that", "this", "enzyme", "exhibits", "absolute", "specificity", "to", "catechol", "C-3", "substituents", "(Kieboom", "et", "al.", "2001)", "and", "clearly", "suggests", "dependence", "between", "inductor", "and", "the", "activity", "of", "2,3-", "dioxygenase.", "Cassidy", "et", "al.", "(1999)", "observed", "degradation", "of", "nitrophenols", "by", "Sphingomonas", "sp.", "strain", "UG30", "after", "induction", "of", "hydroquinone", "dioxygenase", "by", "pentachloro-", "phenol.", "Pentachlorophenol-induced", "enzyme", "transformed", "benzenotriol", "formed", "during", "p-nitrophenol", "degradation.", "Because", "of", "high", "toxicity", "and", "resistance", "to", "biodegradation,", "mononitrophenols", "are", "insufficient", "source", "of", "carbon", "and", "energy", "for", "microorganisms", "and", "degradation", "of", "these", "123" ]

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[ "Nicodemo", "et", "al.", "Molecular", "Brain", "2010,", "3:4", "http://www.molecularbrain.com/content/3/1/4", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Pyk2", "uncouples", "metabotropic", "glutamate", "receptor", "G", "protein", "signaling", "but", "facilitates", "ERK1/2", "activation", "Alexander", "A", "Nicodemo1,", "Macarena", "Pampillo1,", "Lucimar", "T", "Ferreira1,", "Lianne", "B", "Dale1,", "Tamara", "Cregan1,", "Fabiola", "M", "Ribeiro1,", "Stephen", "SG", "Ferguson1,2*", "Abstract", "Group", "I", "metabotropic", "glutamate", "receptors", "(mGluRs)", "are", "coupled", "via", "Gaq/11", "to", "the", "activation", "of", "phospholipase", "Cb,", "which", "hydrolyzes", "membrane", "phospholipids", "to", "form", "inositol", "1,4,5", "trisphosphate", "and", "diacylglycerol.", "This", "results", "in", "the", "release", "of", "Ca2+", "from", "intracellular", "stores", "and", "the", "activation", "of", "protein", "kinase", "C.", "The", "activation", "of", "Group", "I", "mGluRs", "also", "results", "in", "ERK1/2", "phosphorylation.", "We", "show", "here,", "that", "the", "proline-rich", "tyrosine", "kinase", "2", "(Pyk2)", "inter-", "acts", "with", "both", "mGluR1", "and", "mGluR5", "and", "is", "precipitated", "with", "both", "receptors", "from", "rat", "brain.", "Pyk2", "also", "interacts", "with", "GST-fusion", "proteins", "corresponding", "to", "the", "second", "intracellular", "loop", "and", "the", "distal", "carboxyl-terminal", "tail", "domains", "of", "mGluR1a.", "Pyk2", "colocalizes", "with", "mGluR1a", "at", "the", "plasma", "membrane", "in", "human", "embryonic", "kidney", "(HEK293)", "cells", "and", "with", "endogenous", "mGluR5", "in", "cortical", "neurons.", "Pyk2", "overexpression", "in", "HEK293", "results", "in", "attenuated", "basal", "and", "ago-", "nist-stimulated", "inositol", "phosphate", "formation", "in", "mGluR1", "expressing", "cells", "and", "involves", "a", "mechanism", "whereby", "Pyk2", "displaces", "Gaq/11", "from", "the", "receptor.", "The", "activation", "of", "endogenous", "mGluR1", "in", "primary", "mouse", "cortical", "neuron", "stimu-", "lates", "ERK1/2", "phosphorylation.", "Treatments", "that", "prevent", "Pyk2", "phosphorylation", "in", "cortical", "neurons,", "and", "the", "overex-", "pression", "of", "Pyk2", "dominant-negative", "and", "catalytically", "inactive", "Pyk2", "mutants", "in", "HEK293", "cells,", "prevent", "ERK1/2", "phosphorylation.", "The", "Pyk2", "mediated", "activation", "of", "ERK1/2", "phosphorylation", "is", "also", "Src-,", "calmodulin-", "and", "protein", "kinase", "C-dependent.", "Our", "data", "reveal", "that", "Pyk2", "couples", "the", "activation", "mGluRs", "to", "the", "mitogen-activated", "protein", "kinase", "pathway", "even", "though", "it", "attenuates", "mGluR1-dependent", "G", "protein", "signaling.", "Background", "Glutamate", "is", "the", "predominant", "excitatory", "neurotransmit-", "ter", "in", "the", "brain", "and", "regulates", "physiological", "responses", "that", "include", "the", "development,", "survival,", "and", "death", "of", "neurons", "as", "well", "as", "neural", "plasticity", "[1-6].", "The", "receptors", "that", "respond", "to", "glutamate", "can", "be", "classified", "into", "two", "types:", "ionotropic", "and", "metabotropic.", "Ionotropic", "gluta-", "mate", "receptors", "are", "comprised", "of", "cation-specific", "ion", "channels", "that", "can", "be", "subclassified", "into", "NMDA,", "AMPA", "and", "kainate", "receptors.", "In", "contrast,", "metabotropic", "gluta-", "mate", "receptors", "(mGluRs)", "are", "coupled", "to", "the", "activation", "of", "heterotrimeric", "G", "proteins", "and", "the", "regulation", "of", "intra-", "cellular", "second", "messenger", "levels.", "They", "are", "subcategor-", "ized", "into", "three", "groups", "based", "on", "sequence", "similarity", "and", "*", "Correspondence:", "ferguson@robarts.ca", "1J", "Allyn", "Taylor", "Centre", "for", "Cell", "Biology,", "Molecular", "Brain", "Research", "Group,", "Robarts", "Research", "Institute,", "The", "University", "of", "Western", "Ontario,", "100", "Perth", "Dr,", "London,", "ON,", "N6A", "5K8,", "Canada", "G", "protein", "specificity", "[1].", "Group", "I", "mGluRs", "(mGluR1", "and", "mGluR5)", "are", "coupled", "to", "Gaq/11", "and", "the", "activation", "of", "phospholipase", "Cb", "which", "in", "turn", "stimulates", "the", "forma-", "tion", "of", "the", "intracellular", "second", "messengers,", "inositol", "1,4,5-triphosphate", "(InsP3)", "and", "diacylglycerol.", "InsP3", "sti-", "mulates", "the", "release", "of", "Ca2+", "from", "intracellular", "stores", "and", "both", "Ca2+", "and", "diacylglycerol", "regulate", "the", "activation", "of", "protein", "kinase", "C", "(PKC).", "Agonist-activated", "G", "protein-coupled", "receptors", "(GPCRs)", "function", "as", "guanine", "nucleotide", "exchange", "fac-", "tors", "facilitating", "the", "exchange", "of", "GDP", "for", "GTP", "on", "the", "Ga", "subunit.", "Thus,", "allowing", "the", "dissociation", "of", "the", "Ga", "and", "Gbg", "subunits,", "which", "function", "to", "regulate", "different", "effector", "enzymes", "and", "ion", "channels", "[7].", "The", "activity", "of", "Group", "I", "mGluRs", "is", "regulated", "by", "protein", "kinases", "that", "uncouple", "the", "receptors", "from", "heterotrimeric", "G", "proteins", "via", "both", "phosphorylation-dependent-", "and", "phosphoryla-", "tion-independent", "mechanisms", "[8,9].", "Both", "PKC", "and", "G", "©", "2010", "Nicodemo", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "6-Fluoro-1,3,4-triphenyl-1H-pyrazolo-", "[3,4-b]quinoline", "benzene", "hemisolvate", "Paweł", "Szlachcica*", "and", "Katarzyna", "Stadnickab", "aDepartment", "of", "Chemistry", "and", "Physics,", "Agricultural", "University,", "30-149", "Krako´", "w,", "Poland,", "and", "bFaculty", "of", "Chemistry,", "Jagiellonian", "University,", "30-060", "Krako´", "w,", "Poland", "Correspondence", "e-mail:", "pszlachcic@ar.krakow.pl", "Received", "4", "January", "2010;", "accepted", "4", "February", "2010", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "293", "K,", "P", "=", "98.6", "kPa;", "mean", "(C–C)", "=", "0.004", "A˚;", "R", "factor", "=", "0.064;", "wR", "factor", "=", "0.137;", "data-to-parameter", "ratio", "=", "16.2.", "In", "the", "title", "compound,", "C28H18FN3", "0.5C6H6,", "the", "1H-pyra-", "zolo[3,4-b]quinoline", "core", "is", "almost", "planar", "(r.m.s", "=", "0.0371", "A˚", ",", "maximum", "deviation", "=", "0.0571", "A˚", ")", "and", "aromatic.", "The", "solvent", "benzene", "molecules", "are", "located", "around", "inversion", "centres.", "In", "the", "crystal,", "molecules", "related", "by", "centres", "of", "symmetry", "form", "dimers,", "with", "distances", "of", "3.932", "(3)", "A˚", "between", "best", "planes", "through", "the", "fused", "core", "due", "to", "stacking.", "The", "phenyl", "substituents", "at", "positions", "1,", "3", "and", "4,", "are", "twisted", "away", "from", "the", "core,", "making", "dihedral", "angles", "of", "29.66", "(7),", "44.59", "(7)", "and", "67.94", "(6)", ",", "respectively.", "Related", "literature", "For", "the", "synthesis", "of", "1H-pyrazolo[3,4-b]quinoline", "derivatives,", "see:", "Chaczatrian", "et", "al.", "(2003,", "2007).", "For", "their", "photophysical", "properties,", "see:", "Gondek", "et", "al.", "(2006).", "For", "the", "use", "of", "a", "fluorine", "derivative", "of", "1H-pyrazolo[3,4-b]quinoline", "in", "organic", "light-", "emitting", "diode", "preparation,", "see:", "Tao", "et", "al.", "(2001).", "For", "the", "effect", "of", "substituents", "on", "aromatic", "ring", "geometry,", "see:", "Domenicano", "et", "al.", "(1975).", "organic", "compounds", "Experimental", "Crystal", "data", "C28H18FN3", "0.5C6H6", "Mr", "=", "454.51", "Monoclinic,", "P21=c", "a", "=", "13.2941", "(4)", "A˚", "b", "=", "9.7419", "(3)", "A˚", "c", "=", "20.7608", "(5)", "A˚", "=", "118.559", "(2)", "Data", "collection", "Nonius", "KappaCCD", "diffractometer", "Absorption", "correction:", "multi-scan", "(HKL", "DENZO", "and", "SCALEPACK;", "Otwinowski", "&", "Minor,", "1997)", "Tmin", "=", "0.968,", "Tmax", "=", "0.998", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.064", "wR(F", "2)", "=", "0.137", "S", "=", "1.06", "5135", "reflections", "317", "parameters", "V", "=", "2361.58", "(12)", "A˚3", "Z", "=", "4", "Mo", "K", "radiation", "=", "0.08", "mm", "1", "T", "=", "293", "K", "0.40", "0.25", "0.03", "mm", "8615", "measured", "reflections", "5135", "independent", "reflections", "2974", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.051", "3", "restraints", "H-atom", "parameters", "constrained", "max", "=", "0.18", "e", "A˚", "3", "min", "=", "0.19", "e", "A˚", "3", "Data", "collection:", "COLLECT", "(Nonius,", "1998);", "cell", "refinement:", "HKL", "SCALEPACK", "(Otwinowski", "&", "Minor,", "1997);", "data", "reduction:", "HKL", "DENZO", "and", "SCALEPACK;", "program(s)", "used", "to", "solve", "structure:", "SIR92", "(Altomare", "et", "al.,", "1994);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEP-3", "(Farrugia,", "1997);", "software", "used", "to", "prepare", "material", "for", "publication:", "SHELXL97.", "The", "authors", "are", "grateful", "to", "the", "Ministry", "of", "Science", "and", "Higher", "Education,", "Poland,", "for", "financial", "support", "of", "this", "work", "through", "grant", "No.", "N", "N204", "216734.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "GK2254).", "References", "Altomare,", "A.,", "Cascarano,", "G.,", "Giacovazzo,", "C.,", "Guagliardi,", "A.,", "Burla,", "M.", "C.,", "Polidori,", "G.", "&", "Camalli,", "M.", "(1994).", "J.", "Appl.", "Cryst.", "27,", "435.", "Chaczatrian,", "K.,", "Chaczatrian,", "G.,", "Danel,", "A.", "&", "Tomasik,", "P.", "(2003).", "Pol.", "J.", "Chem.", "77,", "1141–1147.", "Chaczatrian,", "K.,", "Chaczatrian,", "G.,", "Danel,", "A.", "&", "Tomasik,", "P.", "(2007).", "Polish", "Patent", "PL", "195700", "B1.", "Domenicano,", "A.,", "Vaciago,", "A.", "&", "Coulson,", "C.", "A.", "(1975).", "Acta", "Cryst.", "B31,", "221–", "234.", "Farrugia,", "L.", "J.", "(1997).", "J.", "Appl.", "Cryst.", "30,", "565.", "Gondek,", "E.,", "Kityk,", "I.", "V.,", "Sanetra,", "J.,", "Szlachcic,", "P.,", "Armatys,", "P.,", "Wisla,", "A.", "&", "Danel,", "A.", "(2006).", "Opt.", "Laser", "Technol.", "38,", "487–492.", "Nonius", "(1998).", "COLLECT.", "Nonius", "BV,", "Delft,", "The", "Netherlands.", "Otwinowski,", "Z.", "&", "Minor,", "W.", "(1997).", "Methods", "in", "Enzymology,", "Vol.", "276,", "Macromolecular", "Crystallography,", "Part", "A,", "edited", "by", "C.", "W.", "Carter", "Jr", "&", "R.", "M.", "Sweet,", "pp.", "307–326.", "New", "York:", "Academic", "Press.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Tao,", "Y.", "T.,", "Balasubramaniam,", "E.,", "Danel,", "A.,", "Jarosz,", "B.", "&", "Tomasik,", "P.", "(2001).", "Chem.", "Mater.", "13,", "1207–1212.", "Acta", "Cryst.", "(2010).", "E66,", "o575", "doi:10.1107/S1600536810004496", "Szlachcic", "and", "Stadnicka", "o575" ]

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[ "BMC", "Complementary", "and", "Alternative", "Medicine", "2BR2M0e0Cs2eC,oamrcplhemaernttaicryleand", "Alternative", "Medicine", "x", "Impact", "of", "in", "utero", "exposure", "to", "EtOH", "on", "corpus", "callosum", "development", "and", "paw", "preference", "in", "rats:", "protective", "effects", "of", "silymarin", "Nicol", "Moreland,", "Linda", "La", "Grange*", "and", "Rebecca", "Montoya", "Address:", "Department", "of", "Behavioral", "Sciences,", "New", "Mexico", "Highlands", "University,", "117", "Hewett", "Hall,", "Las", "Vegas,", "NM", "87701", "E-mail:", "Nicol", "Moreland", "-", "nicolmoreland@hotmail.com;", "Linda", "La", "Grange*", "-", "lagrange_l@nmhu.edu;", "Rebecca", "Montoya", "-", "sarahnc7@hotmail.com", "*Corresponding", "author", "Published:", "11", "November", "2002", "BMC", "Complementary", "and", "Alternative", "Medicine", "2002,", "2:10", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1472-6882/2/10", "Received:", "18", "July", "2002", "Accepted:", "11", "November", "2002", "©", "2002", "Moreland", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "article", "is", "published", "in", "Open", "Access:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "per-", "mitted", "in", "all", "media", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "BioMed", "Central", "Open", "Access", "Abstract", "Background:", "Using", "a", "rat", "model", "we", "have", "found", "that", "the", "bioflavonoid", "silymarin", "(SY)", "ameliorates", "some", "of", "the", "negative", "consequences", "of", "in", "utero", "exposure", "to", "ethanol", "(EtOH).", "In", "the", "current", "study", "our", "aim", "was", "to", "determine", "if", "laterality", "preference", "and", "corpus", "callosum", "development", "were", "altered", "in", "rat", "offspring", "whose", "mothers", "were", "provided", "with", "a", "concomitant", "administration", "of", "SY", "with", "EtOH", "throughout", "gestation.", "Methods:", "We", "provided", "pregnant", "Fisher/344", "rats", "with", "liquid", "diets", "containing", "35%", "ethanol", "derived", "calories", "(EDC)", "throughout", "the", "gestational", "period.", "A", "silymarin/phospholipid", "compound", "containing", "29.8%", "silybin", "was", "co", "administered", "with", "EtOH", "to", "a", "separate", "experimental", "group.", "We", "tested", "the", "offspring", "for", "laterality", "preference", "at", "age", "12", "weeks.", "After", "testing", "the", "rats", "were", "sacrificed", "and", "their", "brains", "perfused", "for", "later", "corpus", "callosum", "extraction.", "Results:", "We", "observed", "incomplete", "development", "of", "the", "splenium", "in", "the", "EtOH-only", "offspring.", "Callosal", "development", "was", "complete", "in", "all", "other", "treatment", "groups.", "Rats", "from", "the", "EtOH-only", "group", "displayed", "a", "left", "paw", "preference;", "whereas", "control", "rats", "were", "evenly", "divided", "between", "right", "and", "left", "paw", "preference.", "Inexplicably", "both", "SY", "groups", "were", "largely", "right", "paw", "preferring.", "Conclusions:", "The", "addition", "of", "SY", "to", "the", "EtOH", "liquid", "diet", "did", "confer", "some", "ameliorative", "effects", "upon", "the", "developing", "fetal", "rat", "brain.", "Background", "Fetal", "alcohol", "syndrome", "(FAS)", "children", "do", "not", "display", "the", "normal", "hemispheric", "dominance", "patterns", "observed", "in", "non-FAS", "children", "[1].", "Dominance", "has", "been", "disrupted", "or", "is,", "in", "some", "cases,", "completely", "absent,", "depending", "on", "the", "amount", "of", "tissue", "loss", "in", "the", "corpus", "callosum.", "Morpholog-", "ical", "abnormalities,", "one", "of", "which", "is", "corpus", "callosum", "hypo-", "plasia,", "has", "been", "observed", "in", "children", "with", "FAS", "[2].", "Archibald", "et", "al.", "[3],", "using", "structural", "magnetic", "imaging", "(sMRI),", "also", "noted", "that", "there", "were", "corpus", "callosum", "abnor-", "malities", "in", "children", "who", "had", "experienced", "prenatal", "expo-", "sure", "to", "ethanol.", "In", "a", "magnetic", "resonance", "imaging", "(MRI)", "study", "of", "adult", "FAS", "males,", "callosal", "morphological", "data,", "when", "compared", "with", "landmark", "data,", "differed", "significantly", "from", "that", "of", "control", "males", "[4].", "Agenesis", "of", "the", "corpus", "callosum", "occurs", "as", "a", "consequence", "of", "early", "embryonic", "insult.", "The", "exact", "time", "of", "the", "insult", "usu-", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Expression", "of", "a", "Finger", "Millet", "Transcription", "Factor,", "EcNAC1,", "in", "Tobacco", "Confers", "Abiotic", "Stress-Tolerance", "Venkategowda", "Ramegowda1,2¤,", "Muthappa", "Senthil-Kumar2,", "Karaba", "N.", "Nataraja1,", "Malireddy", "K.", "Reddy3,", "Kirankumar", "S.", "Mysore2,", "Makarla", "Udayakumar1*", "1", "Department", "of", "Crop", "Physiology,", "University", "of", "Agricultural", "Sciences,", "Bangalore,", "Karnataka,", "India,", "2", "Plant", "Biology", "Division,", "The", "Samuel", "Roberts", "Noble", "Foundation,", "Ardmore,", "Oklahoma,", "United", "States", "of", "America,", "3", "International", "Centre", "for", "Genetic", "Engineering", "and", "Biotechnology,", "New", "Delhi,", "Delhi,", "India", "Abstract", "NAC", "(NAM,", "ATAF1-2,", "and", "CUC2)", "proteins", "constitute", "one", "of", "the", "largest", "families", "of", "plant-specific", "transcription", "factors", "and", "have", "been", "shown", "to", "be", "involved", "in", "diverse", "plant", "processes", "including", "plant", "growth,", "development,", "and", "stress-tolerance.", "In", "this", "study,", "a", "stress-responsive", "NAC", "gene,", "EcNAC1,", "was", "isolated", "from", "the", "subtracted", "stress", "cDNA", "library", "generated", "from", "a", "drought", "adapted", "crop,", "finger", "millet,", "and", "characterized", "for", "its", "role", "in", "stress-tolerance.", "The", "expression", "analysis", "showed", "that", "EcNAC1", "was", "highly", "induced", "during", "water-deficit", "and", "salt", "stress.", "EcNAC1", "shares", "high", "amino", "acid", "similarity", "with", "rice", "genes", "that", "have", "been", "phylogenetically", "classified", "into", "stress-related", "NAC", "genes.", "Our", "results", "demonstrated", "that", "tobacco", "transgenic", "plants", "expressing", "EcNAC1", "exhibit", "tolerance", "to", "various", "abiotic", "stresses", "like", "simulated", "osmotic", "stress,", "by", "polyethylene", "glycol", "(PEG)", "and", "mannitol,", "and", "salinity", "stress.", "The", "transgenic", "plants", "also", "showed", "enhanced", "tolerance", "to", "methyl-viologen", "(MV)", "induced", "oxidative", "stress.", "Reduced", "levels", "of", "reactive", "oxygen", "species", "(ROS)", "and", "ROS-induced", "damage", "were", "noticed", "in", "pot", "grown", "transgenic", "lines", "under", "water-deficit", "and", "natural", "high", "light", "conditions.", "Root", "growth", "under", "stress", "and", "recovery", "growth", "after", "stress", "alleviation", "was", "more", "in", "transgenic", "plants.", "Many", "stress-responsive", "genes", "were", "found", "to", "be", "up-regulated", "in", "transgenic", "lines", "expressing", "EcNAC1.", "Our", "results", "suggest", "that", "EcNAC1", "overexpression", "confers", "tolerance", "against", "abiotic", "stress", "in", "susceptible", "species,", "tobacco.", "Citation:", "Ramegowda", "V,", "Senthil-Kumar", "M,", "Nataraja", "KN,", "Reddy", "MK,", "Mysore", "KS,", "et", "al.", "(2012)", "Expression", "of", "a", "Finger", "Millet", "Transcription", "Factor,", "EcNAC1,", "in", "Tobacco", "Confers", "Abiotic", "Stress-Tolerance.", "PLoS", "ONE", "7(7):", "e40397.", "doi:10.1371/journal.pone.0040397", "Editor:", "Keqiang", "Wu,", "National", "Taiwan", "University,", "Taiwan", "Received", "February", "17,", "2012;", "Accepted", "June", "6,", "2012;", "Published", "July", "11,", "2012", "Copyright:", "2012", "Ramegowda", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "has", "been", "supported", "by", "grants", "from", "the", "Department", "of", "Biotechnology", "(Transcription", "factor", "project", "grant", "number", "F.No.BT/PR/4946/Agr/16/", "421/2004,", "Centre", "of", "excellence", "grant", "number", "F.No.", "BT/01/COE/05/03),", "Government", "of", "India", "and", "Indian", "Council", "of", "Agricultural", "Research", "(Niche", "area", "of", "excellence", "grant", "number", "F.No.10-(6)/2005", "EP&D),", "India.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "udayakumar_m@yahoo.com", "¤", "Current", "address:", "Department", "of", "Crop,", "Soil", "and", "Environmental", "Sciences,", "University", "of", "Arkansas,", "Fayetteville,", "Arkansas,", "United", "States", "of", "America", "Introduction", "Plants", "maintain", "cellular", "homeostasis", "under", "abiotic", "stress", "by", "adjusting", "their", "metabolic", "systems.", "The", "early", "events", "of", "plant", "adaptation", "to", "the", "environmental", "stresses", "involve", "stress-signal", "perception", "and", "transduction", "leading", "to", "the", "expression", "of", "stress-", "responsive", "genes", "and", "activation", "of", "various", "physiological", "and", "metabolic", "responses", "[1],", "[2],", "[3].", "The", "products", "of", "stress-responsive", "genes", "can", "either", "directly", "protect", "cells", "against", "abiotic", "stress", "or", "regulate", "the", "expression", "of", "other", "genes.", "The", "stress", "regulatory", "molecules,", "including", "mitogen-activated", "protein", "kinases,", "histidine", "kinases,", "Ca2+-dependent", "protein", "kinases,", "as", "well", "as", "transcription", "factors", "are", "well", "characterized", "[4],", "[5].", "The", "expression", "of", "stress-", "responsive", "genes", "is", "largely", "governed", "by", "specific", "transcription", "factors.", "Stress-responsive", "transcription", "factors", "predominantly", "interact", "with", "promoter", "elements", "of", "stress", "genes", "often", "resulting", "in", "expression", "of", "many", "functional", "genes.", "This", "has", "been", "elegantly", "shown", "for", "DREB", "and", "bZIP", "transcription", "factors", "which", "recognize", "drought", "responsible", "element", "(DRE)", "and", "the", "abscisic", "acid", "responsive", "element", "(ABRE),", "respectively,", "and", "activate", "an", "array", "of", "stress", "genes", "[6].", "Several", "families", "of", "transcription", "factors,", "including", "ERF/AP2,", "HSF,", "bZIP,", "MYB,", "MYC,", "NAC,", "WRKY,", "and", "Zinc-finger,", "have", "been", "well", "characterized", "for", "their", "regulatory", "roles", "in", "eliciting", "plant", "stress-responses", "[5],", "[7–10].", "NAC", "family", "proteins", "are", "plant-specific", "transcription", "factors", "that", "are", "characterized", "by", "a", "conserved", "DNA-binding", "NAC", "domain", "located", "in", "the", "N-terminal", "region", "and", "a", "variable", "C-terminal", "domain", "[11].", "Although", "the", "genomes", "of", "rice", "and", "Arabidopsis", "were", "predicted", "to", "contain", "140", "and", "75", "NAC", "genes,", "respectively,", "[12],", "[13],", "only", "a", "few", "members", "of", "this", "large", "family", "have", "been", "characterized", "and", "most", "of", "them", "were", "reported", "to", "be", "involved", "in", "plant", "growth,", "development,", "and", "hormone", "signaling", "[14].", "Recently,", "a", "few", "NAC", "proteins", "have", "been", "described", "as", "mediators", "of", "biotic", "and", "abiotic", "stress", "signaling.", "Expression", "analysis", "showed", "that", "NAC", "genes,", "such", "as", "ANAC019,", "ANAC055,", "and", "ANAC072", "from", "Arabidopsis", "[15],", "and", "BnNAC", "from", "Brassica", "napus", "[16],", "were", "induced", "by", "various", "environmental", "stresses.", "Furthermore,", "overexpression", "of", "a", "few", "NAC", "genes", "has", "been", "shown", 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[ "dAtaxin-2", "Mediates", "Expanded", "Ataxin-1-Induced", "Neurodegeneration", "in", "a", "Drosophila", "Model", "of", "SCA1", "Ismael", "Al-Ramahi1,2,", "Alma", "M.", "Pe´", "rez1,", "Janghoo", "Lim1,", "Minghang", "Zhang1,", "Rie", "Sorensen1,", "Maria", "de", "Haro1,", "Joana", "Branco1,", "Stefan", "M.", "Pulst3,", "Huda", "Y.", "Zoghbi1,4,5,", "Juan", "Botas1*", "1", "Department", "of", "Molecular", "and", "Human", "Genetics,", "Baylor", "College", "of", "Medicine,", "Houston,", "Texas,", "United", "States", "of", "America,", "2", "Departamento", "de", "Biolog´ıa,", "Facultad", "de", "Ciencias-", "University", "Autonoma", "de", "Madrid,", "Madrid,", "Spain,", "3", "Division", "of", "Neurology,", "Cedars-Sinai", "Medical", "Center;", "Departments", "of", "Medicine", "and", "Neurobiology,", "David", "Geffen", "School", "of", "Medicine,", "University", "of", "California", "at", "Los", "Angeles,", "Los", "Angeles,", "California,", "United", "States", "of", "America,", "4", "Department", "of", "Neuroscience,", "Baylor", "College", "of", "Medicine,", "Houston,", "Texas,", "United", "States", "of", "America,", "5", "Howard", "Hughes", "Medical", "Institute,", "Baylor", "College", "of", "Medicine,", "Houston,", "Texas,", "United", "States", "of", "America.", "Spinocerebellar", "ataxias", "(SCAs)", "are", "a", "genetically", "heterogeneous", "group", "of", "neurodegenerative", "disorders", "sharing", "atrophy", "of", "the", "cerebellum", "as", "a", "common", "feature.", "SCA1", "and", "SCA2", "are", "two", "ataxias", "caused", "by", "expansion", "of", "polyglutamine", "tracts", "in", "Ataxin-1", "(ATXN1)", "and", "Ataxin-2", "(ATXN2),", "respectively,", "two", "proteins", "that", "are", "otherwise", "unrelated.", "Here,", "we", "use", "a", "Drosophila", "model", "of", "SCA1", "to", "unveil", "molecular", "mechanisms", "linking", "Ataxin-1", "with", "Ataxin-2", "during", "SCA1", "pathogenesis.", "We", "show", "that", "wild-type", "Drosophila", "Ataxin-2", "(dAtx2)", "is", "a", "major", "genetic", "modifier", "of", "human", "expanded", "Ataxin-1", "(Ataxin-", "1[82Q])", "toxicity.", "Increased", "dAtx2", "levels", "enhance,", "and", "more", "importantly,", "decreased", "dAtx2", "levels", "suppress", "Ataxin-", "1[82Q]-induced", "neurodegeneration,", "thereby", "ruling", "out", "a", "pathogenic", "mechanism", "by", "depletion", "of", "dAtx2.", "Although", "Ataxin-2", "is", "normally", "cytoplasmic", "and", "Ataxin-1", "nuclear,", "we", "show", "that", "both", "dAtx2", "and", "hAtaxin-2", "physically", "interact", "with", "Ataxin-1.", "Furthermore,", "we", "show", "that", "expanded", "Ataxin-1", "induces", "intranuclear", "accumulation", "of", "dAtx2/hAtaxin-2", "in", "both", "Drosophila", "and", "SCA1", "postmortem", "neurons.", "These", "observations", "suggest", "that", "nuclear", "accumulation", "of", "Ataxin-2", "contributes", "to", "expanded", "Ataxin-1-induced", "toxicity.", "We", "tested", "this", "hypothesis", "engineering", "dAtx2", "transgenes", "with", "nuclear", "localization", "signal", "(NLS)", "and", "nuclear", "export", "signal", "(NES).", "We", "find", "that", "NLS-dAtx2,", "but", "not", "NES-dAtx2,", "mimics", "the", "neurodegenerative", "phenotypes", "caused", "by", "Ataxin-1[82Q],", "including", "repression", "of", "the", "proneural", "factor", "Senseless.", "Altogether,", "these", "findings", "reveal", "a", "previously", "unknown", "functional", "link", "between", "neurodegenerative", "disorders", "with", "common", "clinical", "features", "but", "different", "etiology.", "Citation:", "Al-Ramahi", "I,", "Pe´rez", "AM,", "Lim", "J,", "Zhang", "M,", "Sorensen", "R,", "et", "al.", "(2007)", "dAtaxin-2", "mediates", "expanded", "Ataxin-1-induced", "neurodegeneration", "in", "a", "Drosophila", "model", "of", "SCA1.", "PLoS", "Genet", "3(12)", "e234.", "doi:10.1371/journal.pgen.0030234", "Introduction", "Inherited", "ataxias", "are", "a", "genetically", "heterogeneous", "group", "of", "neurodegenerative", "diseases", "characterized", "by", "loss", "of", "motor", "coordination", "and", "balance.", "They", "can", "be", "caused", "by", "loss-of-", "function", "or", "gain-of-function", "mechanisms;", "some", "ataxias", "are", "triggered", "by", "missense", "mutations,", "while", "others", "by", "triplet", "repeat", "expansions,", "which", "may", "occur", "either", "in", "coding", "or", "non-", "coding", "sequences.", "Furthermore,", "the", "gene", "products", "impli-", "cated", "in", "the", "different", "ataxias", "do", "not", "share", "obvious", "functional", "or", "structural", "relationships", "to", "each", "other.", "In", "spite", "of", "this", "genetic", "heterogeneity,", "many", "ataxias", "show", "striking", "similarities.", "In", "particular,", "it", "is", "often", "difficult", "to", "distinguish", "between", "Spinocerebellar", "ataxias", "(SCAs)", "based", "only", "on", "clinical", "and", "pathological", "observations,", "and", "their", "differential", "diagnosis", "often", "requires", "genetic", "testing.", "In", "addition,", "a", "common", "neuropathological", "feature", "of", "SCAs", "is", "the", "atrophy", "of", "the", "cerebellar", "module", "(reviewed", "in", "[1–3]).", "These", "similarities", "suggest", "that", "SCAs,", "and", "perhaps", "other", "ataxias,", "may", "also", "share", "common", "mechanisms", "of", "pathogenesis.", "In", "support", "of", "this", "hypothesis", "a", "recent", "study", "reported", "a", "network", "of", "physical", "protein-protein", "interactions", "among", "many", "factors", "associated", "with", "ataxia", "and", "Purkinje", "cell", "degeneration", "in", "humans", "and", "mice", "[4].", "However,", "no", "specific", "molecular", "mechanisms", "are", "known", "that", "can", "account", "for", "the", "clinical", "and", "neuoropatho-", "logical", "similarities", "among", "SCAs", "and", "other", "ataxias.", "SCA1", "is", "caused", "by", "the", "expansion", "of", "a", "CAG", "repeat", "encoding", "a", "polyglutamine", "tract", "in", "the", "protein", "Ataxin-1", "that", "induces", "a", "toxic", "gain", "of", "function", "[5].", "The", "expanded", "protein", "accumulates", "in", "neuronal", "nuclear", "inclusions", "(NIs)", "that", "also", "contain", "tran-", "scription", "factors,", "chaperones,", "proteasome", "subunits,", "and", "other", "components", "of", "the", "protein", "quality", "control/degradation", "machinery", "like", "CHIP", "or", "Ataxin-3", "[6–11].", "Abnormally", "long", "polyglutamine", "tracts", "are", "the", "common", "cause", "of", "pathogenesis", "in", "at", "least", "five", "other", "SCAs", "(SCA2,", "3,", "6,", "7", "and", "17)", "and", "three", "additional", "neurodegenerative", "diseases", "including", "Hunting-", "ton’s", "disease", "(HD)", "[1,12].", "Protein", "quality", "control", "machinery", "as", "well", "as", "transcriptional", "dysregulation", "are", "general", "mechanisms", "that", "have", "been", "implicated", "in", "the", "pathogenesis", "of", "these", "polyglutamine", "disorders", "[13–15].", "Although", "the", "polyglutamine", "expansion", "triggers", "the", "toxicity", "Editor:", "Harry", "Orr,", "University", "of", "Minnesota,", "United", "States", "of", "America", "Received", "July", "11,", "2007;", "Accepted", "November", "15,", "2007;", "Published", "December", "28,", "2007", "A", "previous", "version", "of", "this", "article", "appeared", "as", "an", "Early", "Online", "Release", "on", "November", "16,", "2007", "(doi:10.1371/journal.pgen.0030234.eor).", "Copyright:", "2007", "Al-Ramahi", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "*", "To", "whom", "correspondence", "should", "be", "addressed.", "E-mail:", "jbotas@bcm.tmc.edu", "PLoS", "Genetics", "|", "www.plosgenetics.org", "2551", "December", "2007", "|", "Volume", "3", "|", "Issue", "12", "|", "e234" ]

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[ "BMC", "Genomics", "BioMed", "Central", "3BR2M0e0Cs2eG,eanrocmhicsarticle", "x", "Classification", "and", "evolutionary", "history", "of", "the", "single-strand", "annealing", "proteins,", "RecT,", "Redβ,", "ERF", "and", "RAD52", "Lakshminarayan", "M", "Iyer,", "Eugene", "V", "Koonin", "and", "L", "Aravind*", "Address:", "National", "Center", "for", "Biotechnology", "Information,", "National", "Library", "of", "Medicine,", "National", "Institutes", "of", "Health,", "Bethesda,", "MD", "20894,", "USA", "E-mail:", "Lakshminarayan", "M", "Iyer", "-", "lakshmin@ncbi.nlm.nih.gov;", "Eugene", "V", "Koonin", "-", "koonin@ncbi.nlm.nih.gov;", "L", "Aravind*", "-", "aravind@ncbi.nlm.nih.gov", "*Corresponding", "author", "Published:", "21", "March", "2002", "BMC", "Genomics", "2002,", "3:8", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2164/3/8", "Received:", "7", "January", "2002", "Accepted:", "21", "March", "2002", "©", "2002", "Iyer", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "Verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "any", "medium", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Abstract", "Background:", "The", "DNA", "single-strand", "annealing", "proteins", "(SSAPs),", "such", "as", "RecT,", "Redβ,", "ERF", "and", "Rad52,", "function", "in", "RecA-dependent", "and", "RecA-independent", "DNA", "recombination", "pathways.", "Recently,", "they", "have", "been", "shown", "to", "form", "similar", "helical", "quaternary", "superstructures.", "However,", "despite", "the", "functional", "similarities", "between", "these", "diverse", "SSAPs,", "their", "actual", "evolutionary", "affinities", "are", "poorly", "understood.", "Results:", "Using", "sensitive", "computational", "sequence", "analysis,", "we", "show", "that", "the", "RecT", "and", "Redβ", "proteins,", "along", "with", "several", "other", "bacterial", "proteins,", "form", "a", "distinct", "superfamily.", "The", "ERF", "and", "Rad52", "families", "show", "no", "direct", "evolutionary", "relationship", "to", "these", "proteins", "and", "define", "novel", "superfamilies", "of", "their", "own.", "We", "identify", "several", "previously", "unknown", "members", "of", "each", "of", "these", "superfamilies", "and", "also", "report,", "for", "the", "first", "time,", "bacterial", "and", "viral", "homologs", "of", "Rad52.", "Additionally,", "we", "predict", "the", "presence", "of", "aberrant", "HhH", "modules", "in", "RAD52", "that", "are", "likely", "to", "be", "involved", "in", "DNA-", "binding.", "Using", "the", "contextual", "information", "obtained", "from", "the", "analysis", "of", "gene", "neighborhoods,", "we", "provide", "evidence", "of", "the", "interaction", "of", "the", "bacterial", "members", "of", "each", "of", "these", "SSAP", "superfamilies", "with", "a", "similar", "set", "of", "DNA", "repair/recombination", "protein.", "These", "include", "different", "nucleases", "or", "Holliday", "junction", "resolvases,", "the", "ABC", "ATPase", "SbcC", "and", "the", "single-strand-binding", "protein.", "We", "also", "present", "evidence", "of", "independent", "assembly", "of", "some", "of", "the", "predicted", "operons", "encoding", "SSAPs", "and", "in", "situ", "displacement", "of", "functionally", "similar", "genes.", "Conclusions:", "There", "are", "three", "evolutionarily", "distinct", "superfamilies", "of", "SSAPs,", "namely", "the", "RecT/", "Redβ,", "ERF,", "and", "RAD52,", "that", "have", "different", "sequence", "conservation", "patterns", "and", "predicted", "folds.", "All", "these", "SSAPs", "appear", "to", "be", "primarily", "of", "bacteriophage", "origin", "and", "have", "been", "acquired", "by", "numerous", "phylogenetically", "distant", "cellular", "genomes.", "They", "generally", "occur", "in", "predicted", "operons", "encoding", "one", "or", "more", "of", "a", "set", "of", "conserved", "DNA", "recombination", "proteins", "that", "appear", "to", "be", "the", "principal", "functional", "partners", "of", "the", "SSAPs.", "Introduction", "Homologous", "DNA", "recombination", "is", "a", "fundamental", "proc-", "ess", "in", "the", "biochemistry", "of", "DNA", "repair", "and", "replication,", "which", "contributes", "to", "the", "generation", "of", "the", "genetic", "diversi-", "ty", "critical", "for", "natural", "selection.", "An", "important", "step", "in", "the", "recombination", "process", "is", "the", "pairing", "of", "homologous", "dou-", "Page", "1", "of", "11", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Koupidis", "et", "al.", "Health", "and", "Quality", "of", "Life", "Outcomes", "2011,", "9:67", "http://www.hqlo.com/content/9/1/67", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Health", "related", "quality", "of", "life", "in", "patients", "with", "anogenital", "warts", "Sotirios", "A", "Koupidis1*,", "Electra", "Nicolaidou1,", "Maria", "Hadjivassiliou1,", "Stefanos", "Bellos2,", "Petros", "Skapinakis2,", "Christina", "Stefanaki1,", "Helen", "Papadogeorgakis1", "and", "Andreas", "Katsambas1", "Abstract", "Introduction:", "The", "health-related", "quality-of-life", "(HRQoL)", "instruments", "are", "an", "important", "tool", "for", "the", "evaluation", "of", "medical", "outcomes.", "Sexually", "transmitted", "diseases", "(STDs)", "influence", "the", "patients’", "life.", "We", "aimed", "to", "evaluate", "the", "HRQoL", "in", "patients", "with", "anogenital", "warts", "at", "the", "time", "of", "and", "1", "month", "after", "the", "diagnosis.", "Materials", "and", "methods:", "We", "used", "the", "short-form", "(SF)-36", "questionnaire", "to", "compare", "the", "HRQoL", "of", "91", "patients", "with", "anogenital", "warts", "to", "53", "control", "subjects", "with", "the", "same", "socioeconomic", "characteristics.", "Results:", "There", "was", "no", "statistical", "difference", "in", "the", "overall", "HRQoL", "measurement", "between", "the", "anogenital", "wart", "patients", "and", "controls.", "However,", "there", "was", "an", "improvement", "in", "the", "scales", "of", "vitality", "(65.22", "±", "15.70", "vs.", "69.04", "±", "14.11,", "respectively;", "p", "<", "0.05)", "and", "mental", "health", "(65.00", "±", "20.09", "vs.", "69.43", "±", "18.08,", "respectively;", "p", "<", "0.05)", "in", "anogenital", "warts", "patients", "between", "the", "time", "of", "diagnosis", "and", "1", "month", "later.", "Furthermore,", "there", "was", "a", "significant", "deterioration", "in", "the", "scale", "of", "social", "functioning", "(73.47", "±", "22.18", "vs.", "72.89", "±", "19.28,", "respectively;", "p", "<", "0.05).", "The", "small", "sample", "size", "is", "a", "limitation", "of", "our", "study.", "Conclusions:", "HRQoL", "does", "not", "appear", "to", "be", "influenced", "in", "anogenital", "wart", "patients,", "as", "measured", "by", "the", "generic", "instrument", "SF-36.", "It", "is", "therefore", "important", "to", "develop", "specific", "instruments", "for", "the", "measurement", "of", "HRQoL", "in", "this", "group", "of", "patients.", "Introduction", "Sexually", "transmitted", "diseases", "(STDs)", "are", "a", "group", "of", "dis-", "eases", "that", "are", "transmitted", "through", "sexual", "intercourse", "and", "are", "caused", "by", "a", "wide", "variety", "of", "pathogenic", "micro-", "organisms.", "Until", "this", "day,", "more", "than", "50", "micro-organ-", "isms", "have", "been", "recognised", "as", "a", "cause", "of", "STDs", "[1].", "These", "diseases", "comprise", "a", "global", "challenge", "for", "health", "care", "systems", "[2-4].", "As", "STDs", "have", "reached", "epidemic", "dimensions,", "they", "are", "recognized", "as", "a", "considerable", "threat", "for", "public", "health.", "In", "addition,", "STDs", "are", "a", "cause", "of", "acute", "illness,", "infertility,", "disability", "and", "death,", "with", "serious", "med-", "ical", "and", "psychological", "consequences", "for", "millions", "of", "peo-", "ple.", "The", "STD", "epidemic", "is", "associated", "with", "several", "political,", "socioeconomic,", "behavioural,", "biochemical", "and", "biomedical", "factors.", "According", "to", "the", "World", "Health", "Organization", "and", "Eurostat,", "there", "are", "28", "million", "new", "STD", "cases", "in", "Europe", "*", "Correspondence:", "sotirioskoupidis@yahoo.gr", "1Sexually", "Transmitted", "Infections", "Unit,", "1st", "Department", "of", "Dermatology", "and", "Venereology,", "University", "of", "Athens,", "“Andreas", "Sygros”", "Hospital,", "Athens,", "Greece", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "per", "annum", "[3,4].", "The", "highest", "incidence", "is", "observed", "in", "urban", "populations", "between", "15-35", "years", "of", "age", "[3,4].", "Skin", "diseases", "may", "have", "a", "considerable", "effect", "on", "the", "patient’s", "quality-of-life", "(QoL).", "In", "20-50%", "of", "patients", "with", "skin", "diseases", "in", "secondary", "care,", "the", "decrease", "in", "the", "QoL", "may", "be", "severe", "enough", "to", "classify", "the", "patient", "at", "risk", "of", "developing", "severe", "psychosocial", "impairment", "or", "psy-", "chiatric", "morbidity", "such", "as", "clinical", "depression", "[5-7].", "Human", "papillomavirus", "(HPV)", "infection", "is", "the", "most", "common", "cause", "of", "STDs", "worldwide", "with", "50%", "of", "the", "cases", "involving", "individuals", "aged", "15-25", "years", "[8,9].", "More", "than", "100", "different", "types", "of", "HPV", "have", "been", "identified", "[10],", "30", "or", "40", "of", "which", "can", "infect", "the", "mucosa", "and", "skin", "of", "the", "anogenital", "area", "[11,12].", "Clinically,", "anogenital", "warts", "consist", "of", "epidermal", "and", "dermal", "papules", "or", "nodules", "on", "the", "perineum,", "genitalia,", "crural", "folds", "and", "anus.", "They", "vary", "in", "size", "and", "can", "form", "large,", "exophytic", "(cauliflower-like)", "masses,", "especially", "in", "the", "moist", "envir-", "onment", "of", "the", "perineum.", "Discrete", "1-to", "3-", "mm", "sessile", "warts", "may", "occur", "on", "the", "penile", "shaft.", "Warts", "may", "extend", "©", "2011", "Koupidis", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Copyedited", "by:", "ES", "MANUSCRIPT", "CATEGORY:", "ORIGINAL", "PAPER", "BIOINFORMATICS", "ORIGINAL", "PAPER", "Vol.", "28", "no.", "7", "2012,", "pages", "929–937", "doi:10.1093/bioinformatics/bts065", "Gene", "expression", "Advance", "Access", "publication", "February", "13,", "2012", "Positional", "correlation", "analysis", "improves", "reconstruction", "of", "full-length", "transcripts", "and", "alternative", "isoforms", "from", "noisy", "array", "signals", "or", "short", "reads", "Shuji", "Kawaguchi1,", "Kei", "Iida", "1", ",", "Erimi", "Harada", "1", ",", "Kousuke", "Hanada1,2,", "Akihiro", "Matsui2,", "Masanori", "Okamoto2,†,", "Kazuo", "Shinozaki2,", "Motoaki", "Seki2", "and", "Tetsuro", "Toyoda1,∗", "1Bioinformatics", "and", "Systems", "Engineering", "division,", "RIKEN", "Yokohama", "Institute", "and", "2RIKEN", "Plant", "Science", "Center,", "1-7-22", "Suehiro-cho,", "Tsurumi,", "Yokohama,", "Kanagawa", "230-0045,", "Japan", "Associate", "Editor:", "Ivo", "Hofacker", "ABSTRACT", "Motivation:", "A", "reconstruction", "of", "full-length", "transcripts", "observed", "by", "next-generation", "sequencer", "or", "tiling", "arrays", "is", "an", "essential", "technique", "to", "know", "all", "phenomena", "of", "transcriptomes.", "Several", "techniques", "of", "the", "reconstruction", "have", "been", "developed.", "However,", "problems", "of", "high-", "level", "noises", "and", "biases", "still", "remain", "and", "interrupt", "the", "reconstruction.", "A", "method", "is", "required", "that", "is", "robust", "against", "noise", "and", "bias", "and", "correctly", "reconstructs", "transcripts", "regardless", "of", "equipment", "used.", "Results:", "We", "propose", "a", "completely", "new", "statistical", "method", "that", "reconstructs", "full-length", "transcripts", "and", "can", "be", "applied", "on", "both", "next-generation", "sequencers", "and", "tiling", "arrays.", "The", "method", "called", "ARTADE2", "analyzes", "‘positional", "correlation’,", "meaning", "correlations", "of", "expression", "values", "for", "every", "combination", "on", "genomic", "positions", "of", "multiple", "transcriptional", "data.", "ARTADE2", "then", "reconstructs", "full-length", "transcripts", "using", "a", "logistic", "model", "based", "on", "the", "positional", "correlation", "and", "the", "Markov", "model.", "ARTADE2", "elucidated", "17", "591", "full-length", "transcripts", "from", "55", "transcriptome", "datasets", "and", "showed", "notable", "performance", "compared", "with", "other", "recent", "prediction", "methods.", "Moreover,", "1489", "novel", "transcripts", "were", "discovered.", "We", "experimentally", "tested", "16", "novel", "transcripts,", "among", "which", "14", "were", "confirmed", "by", "reverse", "transcription–polymerase", "chain", "reaction", "and", "sequence", "mapping.", "The", "method", "also", "showed", "notable", "performance", "for", "reconstructing", "of", "mRNA", "observed", "by", "a", "next-generation", "sequencer.", "Moreover,", "the", "positional", "correlation", "and", "factor", "analysis", "embedded", "in", "ARTADE2", "successfully", "detected", "regions", "at", "which", "alternative", "isoforms", "may", "exist,", "and", "thus", "are", "expected", "to", "be", "applied", "for", "discovering", "transcript", "biomarkers", "for", "a", "wide", "range", "of", "disciplines", "including", "preemptive", "medicine.", "Availability:", "http://matome.base.riken.jp", "Contact:", "toyoda@base.riken.jp", "Supplementary", "information:", "Supplementary", "data", "are", "available", "at", "Bioinformatics", "online.", "Received", "on", "July", "4,", "2011;", "revised", "on", "January", "25,", "2012;", "accepted", "on", "January", "30,", "2012", "∗To", "whom", "correspondence", "should", "be", "addressed.", "†Present", "Address:", "Center", "for", "Plant", "Cell", "Biology,", "Department", "of", "Botany", "and", "Plant", "Sciences,", "University", "of", "California,", "Riverside,", "3119A", "IIGB,", "Riverside,", "CA", "92521,", "USA.", "1", "INTRODUCTION", "Every", "cell", "of", "every", "organism", "has", "a", "signature", "set", "of", "RNA", "molecules", "with", "certain", "fractions,", "called", "the", "transcriptome.", "The", "transcriptome", "carries", "out", "specialized", "cell", "activities.", "To", "know", "all", "about", "the", "transcriptome", "is", "an", "essential", "step", "for", "understanding", "life.", "Several", "technologies", "are", "developed", "therefore", "to", "observe", "the", "transcriptome.", "Hybridization-based", "methods", "with", "genome", "tiling", "arrays", "have", "been", "used", "to", "approach", "all", "phenomena", "in", "the", "transcriptome", "for", "species", "such", "as", "humans,", "mice", "or", "Arabidiopsis", "thaliana", "whose", "genome", "sequences", "have", "been", "read", "with", "high", "quality", "(Shoemaker", "et", "al.,", "2001;", "Yamada", "et", "al.,", "2003).", "On", "the", "other", "hand,", "high-throughput", "sequencers,", "typically", "called", "next-generation", "sequencers", "(NGS),", "are", "emerging", "as", "a", "major", "equipment", "to", "acquire", "information", "about", "transcriptomes", "by", "the", "method", "called", "mRNA-Seq,", "because", "they", "can", "be", "applied", "not", "only", "for", "well-studied", "organisms", "but", "also", "for", "other", "exotic", "organisms", "(Mizrachi", "et", "al.,", "2010;", "Xu", "et", "al.,", "2011).", "Using", "either", "method,", "a", "reconstruction", "of", "the", "shape", "of", "full-", "length", "RNA/transcripts", "from", "observation", "results", "is", "still", "a", "critical", "step", "in", "the", "study,", "because", "both", "genome", "tiling", "array", "probes", "and", "NGS", "reads", "are", "short", "(<100", "nt)", "and", "represent", "partial", "observations", "of", "original", "molecules", "whose", "lengths", "are", "1000", "nt", "and", "more.", "There", "are", "several", "computational", "programs", "that", "address", "this", "issue.", "We", "have", "also", "developed", "ARTADE1,", "an", "abbreviation", "for", "‘ARabidopsis", "Tiling-Array-based", "Detection", "of", "Exons’—the", "previous", "version", "of", "ARTADE,", "to", "reconstruct", "the", "shape", "of", "mRNA", "molecules", "based", "on", "genome", "information", "and", "mRNA", "expression", "profiles", "from", "genome", "tiling", "arrays", "(Toyoda", "and", "Shinozaki,", "2005).", "Cufflinks", "is", "one", "of", "the", "major", "programs", "applied", "for", "mRNA-", "Seq", "results", "(Trapnell", "et", "al.,", "2010).", "However", "tiling", "array", "and", "mRNA-Seq", "results", "often", "contain", "high", "levels", "of", "noise,", "which", "may", "come", "from", "observation", "machinery", "and", "biological", "fractions", "(Roberts", "et", "al.,", "2011a;", "Royce", "et", "al.,", "2005,", "2007).", "This", "makes", "the", "reconstruction", "of", "full-length", "transcripts", "more", "difficult", "if", "the", "dynamic", "range", "of", "expression", "values", "is", "low.", "Besides,", "it", "is", "known", "that", "amplification,", "hybridization", "and", "sequencing", "biases", "cause", "bad", "effects", "on", "observations.", "Almost", "all", "recent", "methods", "try", "to", "reconstruct", "full-", "length", "transcripts", "by", "only", "using", "transcriptome", "on", "a", "single", "condition.", "We", "think,", "however,", "there", "is", "a", "theoretical", "limit", "to", "the", "extent", "these", "methods", "can", "remove", "noise", "and", "bias.", "©", "The", "Author(s)", "2012.", "Published", "by", "Oxford", "University", "Press.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/3.0),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "[12:32", "12/3/2012", "Bioinformatics-bts065.tex]", "Page:", "929", "929–937" ]

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[ "Hindawi", "Publishing", "Corporation", "Depression", "Research", "and", "Treatment", "Volume", "2011,", "Article", "ID", "836542,", "6", "pages", "doi:10.1155/2011/836542", "Research", "Article", "Relationship", "between", "Depressive", "Symptoms", "and", "Cardiovascular", "Disease", "Risk", "Factors", "in", "African", "American", "Individuals", "Ali", "A.", "Weinstein,1", "Preetha", "Abraham,2", "Guoqing", "Diao,3", "Stacey", "A.", "Zeno,2", "and", "Patricia", "A.", "Deuster2", "1", "Center", "for", "the", "Study", "of", "Chronic", "Illness", "and", "Disability,", "George", "Mason", "University,", "4400", "University", "Drive,", "MSN", "5B7,", "Fairfax,", "VA", "22030,", "USA", "2", "Department", "of", "Military", "and", "Emergency", "Medicine,", "Uniformed", "Services", "University", "of", "the", "Health", "Sciences,", "Bethesda,", "MD", "20814,", "USA", "3", "Department", "of", "Statistics,", "George", "Mason", "University,", "Fairfax,", "VA", "22030,", "USA", "Correspondence", "should", "be", "addressed", "to", "Ali", "A.", "Weinstein,", "aweinst2@gmu.edu", "Received", "25", "January", "2011;", "Revised", "3", "May", "2011;", "Accepted", "17", "June", "2011", "Academic", "Editor:", "Janusz", "K.", "Rybakowski", "Copyright", "©", "2011", "Ali", "A.", "Weinstein", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Objective.", "To", "examine", "the", "relationship", "between", "depressive", "symptoms", "and", "cardiovascular", "disease", "(CVD)", "risk", "factors", "in", "a", "group", "of", "African", "American", "individuals.", "Design.", "A", "nonrandom", "sample", "of", "253", "(age", "43.7", "±", "11.6", "years;", "37%", "male)", "African", "American", "individuals", "was", "recruited", "by", "advertisements.", "Data", "were", "obtained", "by", "validated", "questionnaires,", "anthropometric,", "blood", "pressure,", "and", "blood", "sample", "measurements.", "Results.", "Regression", "analyses", "were", "performed", "to", "assess", "the", "relationship", "between", "depressive", "symptoms", "and", "CVD", "risk", "factors", "controlling", "for", "socioeconomic", "status", "indicators.", "These", "analyses", "demonstrated", "that", "those", "with", "higher", "levels", "of", "depressive", "symptoms", "had", "larger", "waist-to-hip", "ratios,", "higher", "percent", "body", "fat,", "higher", "triglycerides,", "and", "were", "more", "likely", "to", "be", "smokers.", "Conclusions.", "It", "has", "been", "well", "documented", "that", "higher", "levels", "of", "depressive", "symptoms", "are", "associated", "with", "higher", "CVD", "risk.", "However,", "this", "evidence", "is", "derived", "primarily", "from", "samples", "of", "predominantly", "Caucasian", "individuals.", "The", "present", "investigation", "demonstrates", "that", "depressive", "symptoms", "are", "related", "to", "CVD", "risk", "factors", "in", "African", "American", "individuals.", "1.", "Introduction", "African", "Americans", "are", "at", "a", "greater", "risk", "for", "cardiovascular", "disease", "(CVD)", "and", "stroke", "[1],", "having", "higher", "rates", "of", "obesity", "and", "lower", "exercise", "capacity", "[2]", "than", "their", "Caucasian", "counter-", "parts;", "they", "also", "suffer", "premature", "mortality", "because", "of", "CVD", "[1].", "To", "eliminate", "these", "disparities,", "it", "is", "essential", "to", "understand", "why", "these", "differences", "may", "occur.", "Studies", "have", "shown", "that", "socioeconomic", "status", "underlies", "a", "substantial", "portion,", "but", "not", "all,", "of", "the", "higher", "rate", "of", "CVD", "and", "CVD", "consequences", "in", "African", "American", "individuals", "[3].", "However,", "other", "factors", "must", "be", "examined", "to", "try", "to", "explain", "this", "disproportionate", "burden", "of", "CVD.", "The", "factors", "that", "may", "help", "to", "explain", "potential", "health", "disparities", "are", "not", "well", "understood.", "African", "Americans", "may", "be", "at", "an", "increased", "risk", "of", "CVD", "(and", "increased", "consequences", "once", "CVD", "has", "been", "developed)", "due", "to", "increased", "exposure", "to", "stress", "(i.e.,", "racial", "discrimination)", "[4].", "This", "increased", "exposure", "to", "stress", "may", "influence", "mental", "health", "outcomes,", "such", "as", "depression", "[5].", "Depression", "has", "been", "linked", "to", "several", "adverse", "cardiovascular", "outcomes", "and", "may", "be", "important", "to", "consider", "when", "investigating", "potential", "disparities", "in", "CVD.", "In", "addition,", "evidence", "exists", "that", "the", "prevalence", "and", "severity", "of", "depression", "may", "differ", "in", "African", "Americans", "when", "compared", "to", "other", "racial", "groups", "[6].", "Depression", "is", "associated", "with", "several", "physiological", "abnormalities", "that", "could", "contribute", "to", "adverse", "cardiac", "out-", "comes", "[7,", "8].", "Many", "individuals", "with", "depression", "have", "high", "sympathetic", "tone,", "hypercholesterolemia,", "elevated", "cat-", "echolamine", "levels,", "abnormal", "platelet", "activation,", "increased", "inflammatory", "markers,", "and", "endothelial", "dysfunction", "com-", "pared", "to", "persons", "without", "depression", "[9].", "Importantly,", "these", "physiological", "abnormalities", "are", "present", "in", "depressed", "individ-", "uals", "who", "do", "not", "have", "cardiac", "disease", "[10]." ]

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[ "D816–D819", "Nucleic", "Acids", "Research,", "2009,", "Vol.", "37,", "Database", "issue", "doi:10.1093/nar/gkn673", "Published", "online", "5", "October", "2008", "CTdatabase:", "a", "knowledge-base", "of", "high-throughput", "and", "curated", "data", "on", "cancer-testis", "antigens", "Luiz", "Gonzaga", "Almeida1,", "Noboru", "J.", "Sakabe2,", "Alice", "R.", "deOliveira1,", "Maria", "Cristina", "C.", "Silva1,", "Alex", "S.", "Mundstein1,", "Tzeela", "Cohen3,", "Yao-Tseng", "Chen3,", "Ramon", "Chua3,", "Sita", "Gurung3,", "Sacha", "Gnjatic3,", "Achim", "A.", "Jungbluth3,", "Ot", "a´via", "L.", "Caballero3,", "Amos", "Bairoch4,", "Eva", "Kiesler3,", "Sarah", "L.", "White3,", "Andrew", "J.", "G.", "Simpson3,", "Lloyd", "J.", "Old3,", "Anamaria", "A.", "Camargo5", "and", "Ana", "Tereza", "R.", "Vasconcelos1,*", "1Laborato´", "rio", "Nacional", "de", "Computac¸", "a˜", "o", "Cientı´fica,", "Petro´", "polis,", "RJ,", "Brazil,", "2Human", "Genetics", "Department,", "University", "of", "Chicago,", "Chicago,", "IL,", "3Ludwig", "Institute", "for", "Cancer", "Research,", "New", "York,", "NY,", "USA,", "4Swiss", "Institute", "of", "Bioinformatics", "(SIB)", "and", "Structural", "Biology", "and", "Bioinformatics", "Department,", "University", "of", "Geneva,", "Geneva,", "Switzerland", "and", "5Ludwig", "Institute", "for", "Cancer", "Research,", "Sa˜", "o", "Paulo,", "SP,", "Brazil", "Received", "August", "14,", "2008;", "Revised", "September", "21,", "2008;", "Accepted", "September", "22,", "2008", "ABSTRACT", "The", "potency", "of", "the", "immune", "response", "has", "still", "to", "be", "harnessed", "effectively", "to", "combat", "human", "cancers.", "However,", "the", "discovery", "of", "T-cell", "targets", "in", "melano-", "mas", "and", "other", "tumors", "has", "raised", "the", "possibility", "that", "cancer", "vaccines", "can", "be", "used", "to", "induce", "a", "therapeu-", "tically", "effective", "immune", "response", "against", "cancer.", "The", "targets,", "cancer-testis", "(CT)", "antigens,", "are", "immu-", "nogenic", "proteins", "preferentially", "expressed", "in", "normal", "gametogenic", "tissues", "and", "different", "histological", "types", "of", "tumors.", "Therapeutic", "cancer", "vaccines", "directed", "against", "CT", "antigens", "are", "currently", "in", "late-stage", "clin-", "ical", "trials", "testing", "whether", "they", "can", "delay", "or", "prevent", "recurrence", "of", "lung", "cancer", "and", "melanoma", "following", "surgical", "removal", "of", "primary", "tumors.", "CT", "antigens", "constitute", "a", "large,", "but", "ill-defined,", "family", "of", "proteins", "that", "exhibit", "a", "remarkably", "restricted", "expression.", "Currently,", "there", "is", "a", "considerable", "amount", "of", "infor-", "mation", "about", "these", "proteins,", "but", "the", "data", "are", "scat-", "tered", "through", "the", "literature", "and", "in", "several", "bioinformatic", "databases.", "The", "database", "presented", "here,", "CTdatabase", "(http://www.cta.lncc.br),", "unifies", "this", "knowledge", "to", "facilitate", "both", "the", "mining", "of", "the", "existing", "deluge", "of", "data,", "and", "the", "identification", "of", "pro-", "teins", "alleged", "to", "be", "CT", "antigens,", "but", "that", "do", "not", "have", "their", "characteristic", "restricted", "expression", "pattern.", "CTdatabase", "is", "more", "than", "a", "repository", "of", "CT", "antigen", "data,", "since", "all", "the", "available", "information", "was", "care-", "fully", "curated", "and", "annotated", "with", "most", "data", "being", "specifically", "processed", "for", "CT", "antigens", "and", "stored", "locally.", "Starting", "from", "a", "compilation", "of", "known", "CT", "antigens,", "CTdatabase", "provides", "basic", "information", "including", "gene", "names", "and", "aliases,", "RefSeq", "acces-", "sion", "numbers,", "genomic", "location,", "known", "splicing", "variants,", "gene", "duplications", "and", "additional", "family", "members.", "Gene", "expression", "at", "the", "mRNA", "level", "in", "normal", "and", "tumor", "tissues", "has", "been", "collated", "from", "publicly", "available", "data", "obtained", "by", "several", "different", "technologies.", "Manually", "curated", "data", "related", "to", "mRNA", "and", "protein", "expression,", "and", "antigen-specific", "immune", "responses", "in", "cancer", "patients", "are", "also", "avail-", "able,", "together", "with", "links", "to", "PubMed", "for", "relevant", "CT", "antigen", "articles.", "INTRODUCTION", "More", "than", "11", "million", "people", "are", "diagnosed", "with", "cancer", "every", "year", "causing", "12.5%", "of", "all", "deaths", "worldwide", "(World", "Health", "Organization,", "2006).", "Novel", "forms", "of", "cancer", "treat-", "ment", "are", "desperately", "needed,", "and", "immunotherapy", "repre-", "sents", "an", "approach", "that", "has", "yet", "to", "be", "fully", "explored.", "One", "form", "of", "immunotherapy", "is", "the", "therapeutic", "cancer", "vaccine", "that", "induces", "the", "immune", "response", "to", "recognize", "and", "destroy", "cancer", "cells.", "Such", "vaccines", "can", "be", "based", "on", "specific", "antigens,", "such", "as", "the", "CT", "antigens", "that", "are", "specifically", "expressed", "in", "tumors", "with", "limited", "expression", "elsewhere", "in", "the", "patient’s", "tissues.", "Advanced", "clinical", "trials", "of", "CT", "anti-", "gens", "are", "underway.", "In", "2007,", "GlaxoSmithKline", "initiated", "the", "largest-ever", "lung", "cancer", "trial", "to", "test", "the", "ability", "of", "a", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+55", "24", "22336065;", "Fax:", "+55", "24", "33", "6124;", "Email:", "atrv@lncc.br", "The", "authors", "wish", "it", "to", "be", "known", "that,", "in", "their", "opinion,", "the", "first", "two", "authors", "should", "be", "regarded", "as", "joint", "First", "Authors.", "2008", "The", "Author(s)", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.0/uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Head", "and", "Neck", "Pathol", "(2009)", "3:54–58", "DOI", "10.1007/s12105-009-0105-6", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Angiomatosis", "in", "the", "Head", "and", "Neck—3", "Case", "Reports", "Smitha", "R.", "Shetty", "Æ", "Sudeendra", "Prabhu", "Received:", "26", "December", "2008", "/", "Accepted:", "26", "January", "2009", "/", "Published", "online:", "15", "February", "2009", "Humana", "2009", "Abstract", "Angiomatosis", "is", "a", "diffuse", "vascular", "lesion", "which", "involves", "a", "large", "segment", "of", "the", "body", "in", "a", "contiguous", "fashion", "involving", "multiple", "tissues", "(e.g.", "subcutis,", "muscle,", "bone,", "adipose", "tissue", "etc.)", "in", "different", "planes.", "Such", "lesions", "usually", "present", "in", "the", "first", "two", "decades", "of", "life", "with", "female", "predilection", "and", "are", "commonly", "seen", "in", "lower", "extremities.", "It", "clinically", "mimics", "hemangioma", "or", "vascular", "malformation", "and", "its", "surgical", "removal", "is", "difficult", "because", "of", "its", "infiltra-", "tive", "nature", "and", "thus", "has", "high", "recurrence", "rate", "(90%).", "Therefore", "a", "precise", "histopathological", "diagnosis", "of", "angio-", "matosis", "is", "important", "to", "achieve", "a", "curative", "resection.", "Histopathologically", "it", "consists", "of", "proliferating", "blood", "ves-", "sels", "of", "varying", "caliber,", "infiltrating", "into", "the", "soft", "tissues.", "Proliferating", "capillaries", "are", "seen", "within", "or", "adjacent", "to", "major", "vessels.", "Few", "cases", "are", "reported", "in", "head", "and", "neck", "region.", "This", "article", "highlights", "three", "unusual", "cases", "of", "angiomatosis", "reported", "as", "benign", "lesions,", "in", "rare", "sites", "such", "as", "the", "malar", "region", "(predominantly", "infiltrating", "the", "adipose", "tissue),", "within", "the", "masseter", "(predominantly", "infiltrating", "the", "muscle)", "and", "in", "the", "mandible", "(infiltrating", "the", "bone).", "His-", "topathological", "differential", "diagnosis", "is", "also", "discussed.", "Keywords", "Angiomatosis", "Infiltrative", "hemangioma", "Hemangioma", "lymphatics", "and", "nerves", "which", "may", "involve", "skin,", "subcuta-", "neous", "tissue,", "skeletal", "muscle", "and", "occasionally", "bone", "[1].", "It", "is", "extremely", "rare", "and", "benign", "but", "a", "clinically", "extensive", "vascular", "lesion", "of", "soft", "tissue", "which", "usually", "becomes", "symptomatic", "during", "childhood", "or", "adolescence", "[2].", "According", "to", "Rao", "and", "Weiss", "[2],", "angiomatosis", "has", "been", "defined", "as", "a", "histologically", "benign", "vascular", "lesion", "that", "affects", "a", "large", "segment", "of", "the", "body", "in", "a", "contiguous", "fashion,", "either", "by", "vertically", "involving", "multiple", "tissue", "types", "(e.g.", "subcutis,", "muscle,", "bone)", "or", "by", "involving", "similar", "types", "of", "tissues", "(e.g.", "multiple", "muscle).", "It", "has", "a", "highly", "characteristic", "but", "not", "totally", "specific", "histologic", "pattern.", "It", "has", "no", "malig-", "nant", "potential,", "but", "because", "of", "its", "infiltrative", "nature,", "it", "could", "be", "misdiagnosed", "as", "a", "malignancy", "using", "imaging", "tech-", "niques.", "For", "these", "reasons", "diagnosis", "based", "on", "clinical", "and", "radiographic", "findings", "in", "correlation", "with", "histologic", "features", "would", "be", "desirable", "[3].", "Its", "diffuse", "infiltrative", "nature", "makes", "surgical", "resection", "difficult;", "hence,", "recurrence", "is", "a", "common", "feature", "in", "angiomatosis", "[2,", "3].", "The", "aim", "of", "this", "paper", "is", "to", "present", "three", "cases", "of", "angi-", "omatosis", "which", "were", "clinically", "mimicking", "hemangioma,", "lipoma", "and", "arteriovenous", "(AV)", "malformation", "at", "rare", "sites", "such", "as", "within", "the", "masseter,", "malar", "region", "and", "in", "the", "mandible,", "respectively.", "The", "histopathological", "differential", "diagnosis", "and", "prognostic", "importance", "of", "angiomatosis", "is", "also", "discussed.", "Introduction", "Angiomatosis", "is", "a", "complex", "vascular", "malformation", "of", "infancy", "and", "childhood", "consisting", "of", "proliferating", "blood", "vessels", "with", "accompanying", "mature", "fat,", "fibrous", "tissue,", "Case", "Reports", "Case", "1", "S.", "R.", "Shetty", "S.", "Prabhu", "(&)", "SDM", "College", "of", "Dental", "Sciences,", "Dharwad,", "India", "e-mail:", "drsudi78@yahoo.co.in", "A", "13-year-old", "female", "presented", "with", "the", "complaint", "of", "swelling", "in", "the", "right", "side", "of", "face", "since", "2", "years.", "The", "swelling", "had", "slowly", "progressed", "in", "size", "during", "the", "period." ]

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[ "Lin", "et", "al.", "BMC", "Gastroenterology", "2012,", "12:7", "http://www.biomedcentral.com/1471-230X/12/7", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Factors", "linked", "to", "severe", "thrombocytopenia", "during", "antiviral", "therapy", "in", "patients", "with", "chronic", "hepatitis", "c", "and", "pretreatment", "low", "platelet", "counts", "Kung-Hung", "Lin1,2,", "Ping-I", "Hsu1,3,", "Hsien-Chung", "Yu1*,", "Chun-Ku", "Lin1,", "Wei-Lun", "Tsai1,", "Wen-Chi", "Chen1,", "Hoi-Hung", "Chan1", "and", "Kwok-Hung", "Lai1", "Abstract", "Background:", "Baseline", "low", "platelet", "count", "(<", "150,000/μL)", "increases", "the", "risk", "of", "on-treatment", "severe", "thrombocytopenia", "(platelet", "count", "<", "50,000/μL)", "in", "patients", "with", "chronic", "hepatitis", "C", "(CHC)", "undergoing", "antiviral", "therapy,", "which", "may", "interrupt", "treatment.", "The", "purpose", "of", "this", "study", "was", "to", "identify", "risk", "factors", "for", "severe", "thrombocytopenia", "during", "treatment", "for", "CHC", "in", "patients", "with", "baseline", "thrombocytopenia.", "Methods:", "Medical", "records", "were", "reviewed", "for", "125", "patients", "with", "CHC", "treated", "with", "antiviral", "therapy", "according", "to", "the", "standard", "of", "care,", "with", "regular", "follow-up", "examinations.", "Early", "platelet", "decline", "was", "defined", "as", "platelet", "decrease", "during", "the", "first", "2", "weeks", "of", "therapy.", "Results:", "Severe", "thrombocytopenia", "developed", "in", "12.8%", "of", "patients", "with", "baseline", "thrombocytopenia,", "and", "predicted", "a", "higher", "therapeutic", "dropout", "rate.", "Multivariate", "analysis", "revealed", "baseline", "platelet", "count", "<", "100,000/μL", "and", "rapid", "early", "platelet", "decline", "(>", "30%", "decline", "in", "the", "first", "2", "weeks)", "were", "significantly", "associated", "with", "severe", "thrombocytopenia", "(P", "<", "0.001", "and", "0.003,", "odds", "ratios,", "179.22", "and", "45.74,", "respectively).", "In", "these", "patients,", "baseline", "PLT", "≥", "100,000/μL", "and", "lack", "of", "rapid", "early", "platelet", "decline", "predicted", "absence", "of", "severe", "thrombocytopenia", "(negative", "predictive", "values", "were", "95.1%", "and", "96.6%,", "respectively).", "In", "contrast,", "baseline", "platelet", "count", "<", "100,000/μL", "combined", "with", "rapid", "early", "platelet", "decline", "predicted", "severe", "thrombocytopenia", "(positive", "predictive", "value", "was", "100%).", "Conclusions:", "For", "patients", "with", "CHC", "on", "antiviral", "therapy,", "baseline", "platelet", "counts", "<", "100,000/μL", "and", "rapid", "early", "platelet", "decline", "can", "identify", "patients", "at", "high", "risk", "of", "developing", "on-treatment", "severe", "thrombocytopenia.", "Keywords:", "HCV,", "peg-IFN-α,", "ribavirin,", "thrombocytopenia", "Background", "Patients", "with", "chronic", "hepatitis", "C", "(CHC)", "treated", "with", "antiviral", "therapy", "consisting", "of", "pegylated", "interferon-a", "(peg-IFN-a)", "and", "ribavirin", "experience", "a", "response", "super-", "ior", "to", "that", "of", "therapies", "used", "in", "the", "past.", "This", "combina-", "tion", "is", "the", "current", "standard", "of", "care", "[1];", "however,", "side", "effects,", "especially", "hematologic", "abnormalities,", "may", "decrease", "both", "therapeutic", "adherence", "and", "the", "therapeutic", "success", "rate.", "Thrombocytopenia", "is", "one", "of", "the", "potential", "hematologic", "abnormalities", "associated", "with", "peg-IFN-a-", "based", "therapy", "[2-4].", "*", "Correspondence:", "hcyu@vghks.gov.tw", "1Division", "of", "Gastroenterology,", "Department", "of", "Internal", "Medicine,", "Kaohsiung", "Veterans", "General", "Hospital,", "Kaohsiung,", "Taiwan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "One", "recent", "study", "reported", "that", "development", "of", "a", "platelet", "count", "<", "50,000/μL", "was", "independently", "associated", "with", "bleeding", "during", "antiviral", "therapy", "[5].", "In", "clinical", "practice,", "there", "is", "no", "approved", "therapy", "for", "reversing", "the", "decline", "in", "platelet", "count,", "even", "though", "some", "anti-thrombocytopenia", "therapies", "are", "currently", "under", "investigation", "[6].", "Reduction", "of", "the", "dose", "of", "peg-IFN-a", "(either", "peg-IFN-a-2a", "or", "peg-", "IFN-a-2b)", "is", "recommended", "for", "patients", "suffering", "from", "platelet", "counts", "<", "50,000/μL,", "and", "cessation", "of", "anti-viral", "treatment", "is", "recommended", "for", "platelet", "counts", "<", "25,000/μL", "[7].", "Discontinuation", "of", "anti-viral", "therapy", "is", "the", "only", "way", "to", "prevent", "progressive", "thrombocytopenia;", "however,", "disconti-", "nuation", "of", "therapy", "may", "reduce", "the", "rate", "of", "viral", "clearance", "and", "sustained", "virological", "response", "(SVR)", "[8].", "©", "2012", "Lin", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "Pathology", "Research", "International", "Volume", "2011,", "Article", "ID", "636495,", "4", "pages", "doi:10.4061/2011/636495", "Clinical", "Study", "Base-Rate", "Error", "in", "the", "Interpretation", "of", "Immunohistochemistry", "Malcolm", "Galloway", "Department", "of", "Cellular", "Pathology,", "Royal", "Free", "Hospital,", "Royal", "Free", "Hampstead", "NHS", "Trust,", "Pond", "Street,", "Hampstead,", "London,", "NW3", "2QG,", "UK", "Correspondence", "should", "be", "addressed", "to", "Malcolm", "Galloway,", "malcolm.galloway@nhs.net", "Received", "10", "February", "2011;", "Revised", "21", "March", "2011;", "Accepted", "23", "March", "2011", "Academic", "Editor:", "Pablo", "A.", "Bejarano", "Copyright", "©", "2011", "Malcolm", "Galloway.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Failure", "to", "appreciate", "the", "importance", "of", "the", "frequency", "of", "a", "disorder", "in", "the", "appropriate", "population", "(the", "base", "rate)", "may", "lead", "to", "the", "misinterpretation", "of", "the", "diagnostic", "significance", "of", "unexpected", "test", "results", "(unexpected", "test", "result", "defined", "in", "this", "context", "as", "a", "test", "result", "that", "is", "positive", "in", "a", "higher", "proportion", "of", "cases", "of", "an", "alternative", "diagnosis", "than", "in", "the", "diagnosis", "considered", "most", "likely", "before", "the", "test).", "This", "study", "aimed", "to", "determine", "whether", "pathologists", "are", "vulnerable", "to", "this", "error.", "Pathologists", "were", "asked", "to", "estimate", "the", "probability", "of", "tumour", "B", "in", "a", "scenario", "in", "which,", "prior", "to", "the", "immunostaining", "result,", "an", "experienced", "pathologist", "considers", "there", "to", "be", "a", "99%", "chance", "that", "the", "patient", "has", "tumour", "A", "and", "a", "1%", "chance", "that", "they", "have", "tumour", "B.", "Antibody", "X", "is", "positive", "in", "80%", "of", "cases", "of", "tumour", "B", "and", "negative", "in", "90%", "of", "cases", "of", "tumour", "A", "and", "is", "positive", "in", "the", "case", "described", "in", "the", "scenario.", "The", "estimates", "made", "by", "consultant", "pathologists", "ranged", "from", "0", "to", "100%", "(mean", "29.7%).", "The", "Bayesian", "answer", "would", "be", "7.5%.", "These", "findings", "suggest", "that", "base-rate", "error", "may", "lead", "some", "pathologists", "to", "overestimate", "the", "implications", "for", "the", "likelihood", "of", "a", "diagnosis", "in", "the", "light", "of", "an", "unexpected", "immunohistochemical", "result.", "1.", "Introduction", "Base-rate", "error", "in", "medical", "diagnosis", "refers", "to", "the", "cognitive", "bias", "in", "which", "doctors", "may", "underestimate", "the", "importance", "of", "the", "frequency", "of", "the", "relevant", "disorder", "in", "the", "appropriate", "population", "(the", "pretest", "probability)", "when", "considering", "the", "implications", "for", "the", "diagnosis", "of", "the", "result", "of", "tests", "which", "have", "less", "than", "100%", "sensitivity", "and", "specificity.", "An", "underappre-", "ciation", "of", "the", "importance", "of", "the", "base", "rate", "has", "been", "shown", "outside", "medical", "practice,", "for", "example,", "in", "the", "interpretation", "of", "fallible", "witness", "evidence", "[1],", "and", "has", "also", "been", "shown", "in", "relation", "to", "the", "interpretation", "of", "diagnostic", "test", "results", "by", "physicians", "[1–3].", "In", "the", "field", "of", "base-rate", "errors", "in", "diagnostic", "interpre-", "tation,", "the", "most", "closely", "studied", "area", "thus", "far", "has", "been", "in", "relation", "to", "mammography.", "Eddy", "has", "previously", "reported", "base-rate", "error", "in", "the", "interpretation", "of", "the", "diagnostic", "con-", "tribution", "of", "mammogram", "results", "by", "physicians", "[3].", "In", "his", "scenario,", "79.2%", "of", "patients", "with", "breast", "cancer", "are", "assumed", "to", "have", "a", "malignant", "result", "on", "mammography", "(sensitivity)", "and", "90.4%", "of", "patients", "without", "cancer", "to", "have", "a", "benign", "mammogram", "result", "(specificity).", "He", "asked", "what", "he", "described", "as", "“an", "informal", "group", "of", "approximately", "100", "physicians”", "what", "the", "probability", "of", "a", "patient", "having", "breast", "cancer", "would", "be", "if", "they", "had", "a", "1%", "risk", "of", "the", "disease", "prior", "to", "the", "mammogram", "but", "had", "a", "malignant", "diagnosis", "on", "mammography.", "In", "this", "scenario,", "the", "mathematically", "correct", "answer", "(by", "Bayesian", "analysis)", "would", "by", "7.7%.", "He", "reported", "that", "approximately", "95%", "of", "physicians", "estimated", "the", "risk", "as", "approximately", "75%", "(almost", "10", "times", "the", "actual", "risk).", "A", "similar", "study", "in", "which", "physicians", "were", "asked", "to", "predict", "the", "probability", "of", "a", "malignant", "lesion", "in", "a", "patient", "with", "a", "positive", "mammogram", "result", "demonstrated", "that", "even", "when", "providing", "their", "own", "individual", "estimates", "for", "the", "sensitivity", "and", "specificity", "of", "mammography", "in", "a", "breast", "mass", "scenario,", "physicians", "consistently", "overestimated", "the", "impact", "of", "a", "positive", "test", "result", "on", "the", "likelihood", "of", "the", "disease", "[4].", "Pathologists", "are", "regularly", "formulating", "differential", "diag-", "noses", "and", "using", "further", "investigations,", "particularly", "immuno-", "histochemistry,", "to", "assist", "in", "the", "selection", "of", "the", "final", "diagnosis.", "This", "process", "could", "be", "regarded", "as", "cognitively", "equivalent", "to", "the", "processes", "involved", "in", "making", "a", "clinical", "differential", "diagnosis", "of", "a", "breast", "mass,", "further", "investigating", "with", "mam-", "mography,", "and", "then", "deciding", "whether", "to", "proceed", "to", "biopsy.", "As", "with", "mammography,", "immunohistochemistry", "will", "rarely" ]

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[ "BMC", "Microbiology", "Research", "article", "par", "genes", "in", "Mycobacterium", "bovis", "and", "Mycobacterium", "smegmatis", "are", "arranged", "in", "an", "operon", "transcribed", "from", "\"SigGC\"", "promoters", "Yveth", "Casart1,", "Elida", "Gamero1,", "Sandra", "Rivera-Gutierrez2,", "Jorge", "A", "González-y-", "Merchand2", "and", "Leiria", "Salazar*1", "BioMed", "Central", "Open", "Access", "Address:", "1Laboratorio", "de", "Biología", "Molecular.", "Departamento", "de", "Biología", "Estructural,", "Instituto", "Venezolano", "de", "Investigaciones", "Científicas", "(IVIC),", "Apartado", "20632,", "Caracas", "1020-A,", "Venezuela", "and", "2Departamento", "de", "Microbiología,", "Escuela", "Nacional", "de", "Ciencias", "Biológicas,", "IPN,", "Mexico", "DF,", "Mexico", "Email:", "Yveth", "Casart", "-", "ycasart@ivic.ve;", "Elida", "Gamero", "-", "egamero@ivic.ve;", "Sandra", "Rivera-Gutierrez", "-", "leiriasalazar@gmail.com;", "Jorge", "A", "González-y-", "Merchand", "-", "jgonzal1212@yahoo.com.mx;", "Leiria", "Salazar*", "-", "leiriasalazar@gmail.com", "*", "Corresponding", "author", "Published:", "27", "March", "2008", "BMC", "Microbiology", "2008,", "8:51", "doi:10.1186/1471-2180-8-51", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2180/8/51", "Received:", "6", "August", "2007", "Accepted:", "27", "March", "2008", "©", "2008", "Casart", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "ParA/Soj", "and", "ParB/Spo0J", "proteins,", "and", "the", "cis-acting", "parS", "site,", "participate", "actively", "in", "chromosome", "segregation", "and", "cell", "cycle", "progression.", "Genes", "homologous", "to", "parA", "and", "parB,", "and", "two", "putative", "parS", "copies,", "have", "been", "identified", "in", "the", "Mycobacterium", "bovis", "BCG", "and", "Mycobacterium", "smegmatis", "chromosomes.", "As", "in", "Mycobacterium", "tuberculosis,", "the", "parA", "and", "parB", "genes", "in", "these", "two", "non-pathogenic", "mycobacteria", "are", "located", "near", "the", "chromosomal", "origin", "of", "replication.", "The", "present", "work", "focused", "on", "the", "determination", "of", "the", "transcriptional", "organisation", "of", "the", "~6", "Kb", "orf60K-parB", "region", "of", "M.", "bovis", "BCG", "and", "M.", "smegmatis", "by", "primer", "extension,", "transcriptional", "fusions", "to", "the", "green", "fluorescence", "protein", "(GFP)", "and", "quantitative", "RT-PCR.", "Results:", "The", "parAB", "genes", "were", "arranged", "in", "an", "operon.", "However,", "we", "also", "found", "promoters", "upstream", "of", "each", "one", "of", "these", "genes.", "Seven", "putative", "promoter", "sequences", "were", "identified", "in", "the", "orf60K-parB", "region", "of", "M.", "bovis", "BCG,", "whilst", "four", "were", "identified", "in", "the", "homologous", "region", "of", "M.", "smegmatis,", "one", "upstream", "of", "each", "open", "reading", "frame", "(ORF).", "Real-time", "PCR", "assays", "showed", "that", "in", "M.", "smegmatis,", "mRNA-parA", "and", "mRNA-parB", "levels", "decreased", "between", "the", "exponential", "and", "stationary", "phases.", "In", "M.", "bovis", "BCG,", "mRNA-parA", "levels", "also", "decreased", "between", "the", "exponential", "and", "stationary", "phases.", "However,", "parB", "expression", "was", "higher", "than", "parA", "expression", "and", "remained", "almost", "unchanged", "along", "the", "growth", "curve.", "Conclusion:", "The", "majority", "of", "the", "proposed", "promoter", "regions", "had", "features", "characteristic", "of", "Mycobacterium", "promoters", "previously", "denoted", "as", "Group", "D.", "The", "-10", "hexamer", "of", "a", "strong", "E.", "coli", "σ70-", "like", "promoter,", "located", "upstream", "of", "gidB", "of", "M.", "bovis", "BCG,", "overlapped", "with", "a", "putative", "parS", "sequence,", "suggesting", "that", "the", "transcription", "from", "this", "promoter", "might", "be", "regulated", "by", "the", "binding", "of", "ParB", "to", "parS.", "Background", "Partitioning", "systems", "were", "first", "characterised", "in", "low", "copy", "number", "plasmids", "of", "Escherichia", "coli.", "In", "general,", "plasmid", "partition", "modules", "encode", "two", "trans-acting", "proteins", "and", "a", "Page", "1", "of", "13", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Molecular", "Cytogenetics", "Case", "report", "Novel", "complex", "translocation", "involving", "5", "different", "chromosomes", "in", "a", "chronic", "myeloid", "leukemia", "with", "Philadelphia", "chromosome:", "a", "case", "report", "Walid", "Al", "Achkar*1,", "Abdulsamad", "Wafa1,2,", "Hasmik", "Mkrtchyan2,", "Faten", "Moassass1,2", "and", "Thomas", "Liehr2", "BioMed", "Central", "Open", "Access", "Address:", "1Molecular", "Biology", "and", "Biotechnology", "Department,", "Human", "Genetics", "Div.,", "Atomic", "Energy", "Commission", "of", "Syria,", "P.O.", "Box", "6091,", "Damascus,", "Syria", "and", "2Jena", "University", "Hospital,", "Institute", "of", "Human", "Genetics", "and", "Anthropology,", "Kollegiengasse", "10,", "D-07743", "Jena,", "Germany", "Email:", "Walid", "Al", "Achkar*", "-", "scientific@aec.org.sy;", "Abdulsamad", "Wafa", "-", "awafa@mail2world.com;", "Hasmik", "Mkrtchyan", "-", "hamk@mti.uni-jena.de;", "Faten", "Moassass", "-", "fmoassass@mail2world.com;", "Thomas", "Liehr", "-", "i8lith@mti.uni-jena.de", "*", "Corresponding", "author", "Published:", "9", "November", "2009", "Molecular", "Cytogenetics", "2009,", "2:21", "doi:10.1186/1755-8166-2-21", "This", "article", "is", "available", "from:", "http://www.molecularcytogenetics.org/content/2/1/21", "Received:", "14", "September", "2009", "Accepted:", "9", "November", "2009", "©", "2009", "Al", "Achkar", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "well-known", "typical", "fusion", "gene", "BCR/ABL", "can", "be", "observed", "in", "connection", "with", "a", "complex", "translocation", "event", "in", "only", "2-10%", "of", "cases", "with", "chronic", "myeloid", "leukemia", "(CML).", "As", "currently", "most", "CML", "cases", "are", "treated", "with", "Imatinib,", "variant", "rearrangements", "have", "in", "general", "no", "specific", "prognostic", "significance,", "though", "the", "emergence", "of", "therapy", "resistance", "remains", "to", "be", "studied.", "Results:", "Here", "we", "report", "an", "exceptional", "CML", "case", "with", "complex", "chromosomal", "aberrations", "not", "observed", "before,", "involving", "a", "5", "chromosome", "translocation", "implying", "chromosomal", "regions", "such", "as", "1q42,", "4p14", "and", "5q31", "besides", "9q34", "and", "22q11.2.", "Conclusion:", "The", "reported", "rearrangement", "developed", "most", "probably", "in", "one", "initial", "step", "and", "had", "no", "influence", "on", "a", "good", "response", "during", "Imatinib", "treatment.", "Introduction", "Chronic", "myeloid", "leukemia", "(CML),", "a", "clonal", "myeloprolif-", "erative", "disease", "is", "known", "to", "develop", "from", "a", "pluripotent", "bone-marrow", "stem", "cell", "following", "the", "typical", "BCR", "and", "ABL", "somatic", "gene", "rearrangement.", "In", "90-95%", "of", "cases", "with", "CML,", "the", "BCR/ABL", "fusion", "gene", "is", "the", "result", "of", "reciprocal", "translocation", "between", "chromosomes", "9", "and", "22", "and", "is", "cytogenetically", "observable", "as", "a", "small", "derivative", "chromo-", "some", "22", "which", "is", "known", "as", "Philadelphia", "(Ph1)", "chromo-", "some", "[1,2].", "In", "a", "Ph-positive", "CML", "expression", "of", "the", "BCR/ABL", "chimeric", "protein", "p210", "with", "an", "increased", "tyrosine", "kinase", "activity", "is", "essential", "for", "multiple", "signaling", "pathways", "to", "confer", "the", "leukemia", "phenotype", "[3].", "Imatinib", "mesylate", "(Glivec,", "for-", "merly", "STI571)", "was", "designed", "specifically", "to", "inhibit", "the", "tyrosine", "kinase", "activity", "of", "the", "bcr/abl", "protein", "and", "other", "tyrosine", "kinases", "such", "as", "c-abl,", "c-kit", "and", "platelet-derived", "growth", "factor", "receptor.", "By", "binding", "to", "an", "active", "site", "of", "the", "tyrosine", "kinase,", "Imatinib", "mesylate", "switches", "off", "down-", "stream", "signaling,", "cells", "stop", "proliferating", "and", "apoptosis", "ensues", "[4].", "Many", "studies", "have", "shown", "a", "high", "efficiency", "of", "Imatinib", "therapy", "to", "achieve", "a", "complete", "or", "major", "cytoge-", "netic", "response,", "i.e.", "0-34%", "Ph-positive", "cells.", "This", "positive", "effect", "may", "be", "achieved", "in", "cases", "with", "simple", "t(9;22),", "and", "complex", "translocations", "resulting", "in", "a", "BCR/ABL", "fusion", "gene,", "as", "well", "as", "in", "cases", "with", "cytogenetic", "clonal", "evolution", "[5,6].", "Page", "1", "of", "4", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Laskar", "et", "al.", "BMC", "Research", "Notes", "2012,", "5:256", "http://www.biomedcentral.com/1756-0500/5/256", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Modeling", "and", "structural", "analysis", "of", "PA", "clan", "serine", "proteases", "Aparna", "Laskar1*,", "Euan", "J", "Rodger2,", "Aniruddha", "Chatterjee2,3", "and", "Chhabinath", "Mandal1", "Abstract", "Background:", "Serine", "proteases", "account", "for", "over", "a", "third", "of", "all", "known", "proteolytic", "enzymes;", "they", "are", "involved", "in", "a", "variety", "of", "physiological", "processes", "and", "are", "classified", "into", "clans", "sharing", "structural", "homology.", "The", "PA", "clan", "of", "endopeptidases", "is", "the", "most", "abundant", "and", "over", "two", "thirds", "of", "this", "clan", "is", "comprised", "of", "the", "S1", "family", "of", "serine", "proteases,", "which", "bear", "the", "archetypal", "trypsin", "fold", "and", "have", "a", "catalytic", "triad", "in", "the", "order", "Histidine,", "Aspartate,", "Serine.", "These", "proteases", "have", "been", "studied", "in", "depth", "and", "many", "three", "dimensional", "structures", "have", "been", "experimentally", "determined.", "However,", "these", "structures", "mostly", "consist", "of", "bacterial", "and", "animal", "proteases,", "with", "a", "small", "number", "of", "plant", "and", "fungal", "proteases", "and", "as", "yet", "no", "structures", "have", "been", "determined", "for", "protozoa", "or", "archaea.", "The", "core", "structure", "and", "active", "site", "geometry", "of", "these", "proteases", "is", "of", "interest", "for", "many", "applications.", "This", "study", "investigated", "the", "structural", "properties", "of", "different", "S1", "family", "serine", "proteases", "from", "a", "diverse", "range", "of", "taxa", "using", "molecular", "modeling", "techniques.", "Results:", "Our", "predicted", "models", "from", "protozoa,", "archaea,", "fungi", "and", "plants", "were", "combined", "with", "the", "experimentally", "determined", "structures", "of", "16", "S1", "family", "members", "and", "used", "for", "analysis", "of", "the", "catalytic", "core.", "Amino", "acid", "sequences", "were", "submitted", "to", "SWISS-MODEL", "for", "homology-based", "structure", "prediction", "or", "the", "LOOPP", "server", "for", "threading-based", "structure", "prediction.", "Predicted", "models", "were", "refined", "using", "INSIGHT", "II", "and", "SCRWL", "and", "validated", "against", "experimental", "structures.", "Investigation", "of", "secondary", "structures", "and", "electrostatic", "surface", "potential", "was", "performed", "using", "MOLMOL.", "The", "structural", "geometry", "of", "the", "catalytic", "core", "shows", "clear", "deviations", "between", "taxa,", "but", "the", "relative", "positions", "of", "the", "catalytic", "triad", "residues", "were", "conserved.", "Some", "highly", "conserved", "residues", "potentially", "contributing", "to", "the", "stability", "of", "the", "structural", "core", "were", "identified.", "Evolutionary", "divergence", "was", "also", "exhibited", "by", "large", "variation", "in", "secondary", "structure", "features", "outside", "the", "core,", "differences", "in", "overall", "amino", "acid", "distribution,", "and", "unique", "surface", "electrostatic", "potential", "patterns", "between", "species.", "Conclusions:", "Encompassing", "a", "wide", "range", "of", "taxa,", "our", "structural", "analysis", "provides", "an", "evolutionary", "perspective", "on", "S1", "family", "serine", "proteases.", "Focusing", "on", "the", "common", "core", "containing", "the", "catalytic", "site", "of", "the", "enzyme,", "this", "analysis", "is", "beneficial", "for", "future", "molecular", "modeling", "strategies", "and", "structural", "analysis", "of", "serine", "protease", "models.", "Keywords:", "Serine", "protease,", "PA", "clan,", "Homology,", "Threading,", "Modeling", "Background", "Serine", "proteases", "represent", "over", "a", "third", "of", "all", "known", "pro-", "teolytic", "enzymes", "and", "are", "implicit", "in", "a", "wide", "range", "of", "physiological", "processes", "including", "digestion,", "immunity,", "blood", "clotting,", "fibrinolysis,", "reproduction", "and", "protein", "folding", "[1].", "The", "proteolytic", "mechanism", "of", "these", "pro-", "teases", "involves", "nucleophilic", "attack", "of", "the", "carbonyl", "atom", "of", "the", "substrate", "peptide", "bond", "by", "a", "catalytic", "serine", "(Ser)", "*", "Correspondence:", "aparnalaskar@gmail.com", "1Indian", "Institute", "of", "Chemical", "Biology", "(CSIR", "Unit,", "Government", "of", "India),", "Kolkata,", "West", "Bengal", "700032,", "India", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "residue", "in", "the", "active", "site", "of", "the", "enzyme.", "In", "addition", "to", "the", "nucleophilic", "Ser", "residue,", "this", "reaction", "is", "dependent", "on", "two", "other", "amino", "acids", "in", "the", "catalytic", "site,", "Histidine", "(His)", "and", "an", "Aspartate", "(Asp)", "that", "together", "form", "what", "is", "referred", "to", "as", "the", "catalytic", "triad", "(or", "a", "dyad", "in", "some", "cases)", "[2].", "The", "presence", "of", "this", "catalytic", "triad", "in", "at", "least", "four", "distinct", "protein", "folds", "indicates", "evolutionary", "success", "in", "four", "different", "contexts", "[3].", "The", "MEROPS", "classification", "system", "(http://merops.san-", "ger.ac.uk/)", "has", "grouped", "proteases", "into", "clans", "that", "typic-", "ally", "have", "structural", "homology", "and/or", "the", "same", "linear", "order", "of", "catalytic", "triad", "residues", "[4].", "Of", "all", "serine", "©", "2012", "Laskar", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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"experimental", "validation.", "We", "have", "also", "studied", "alternative", "splicing", "pattern", "in", "RhoGEF", "domain", "encoding", "orthologues", "gene", "from", "C.", "briggsae", "and", "have", "obtained", "very", "similar", "results.", "These", "new", "unreported", "spliced", "transcripts,", "which", "were", "not", "detected", "through", "conventional", "approaches,", "not", "only", "point", "towards", "the", "extent", "of", "alternative", "splicing", "in", "C.", "elegans", "genes", "but", "also", "emphasize", "towards", "the", "need", "of", "analyzing", "genome", "data", "using", "a", "combinations", "of", "bioinformatics", "tools", "to", "delineate", "all", "possible", "gene", "products.", "Key", "words:", "RhoGEF", "domain;", "computational", "analysis;", "exon", "prediction;", "alternative", "splicing;", "C.", "elegans;", "C.", "briggsae", "Background:", "The", "guanine", "nucleotide", "exchange", "factors", "for", "the", "Rho", "GTPases", "(RhoGEFs)", "are", "a", "large", "family", "of", "proteins", "that", "share", "a", "dual", "structural", "motif", "designated", "the", "DH/PH", "domain.", "RhoGEFs", "are", "regulators", "of", "the", "Rho", "proteins", "[1]", "that", "act", "as", "molecular", "switches;", "cycling", "between", "inactive", "(GDP-bound)", "and", "active", "(GTP-bound)", "states.", "[2]", "The", "interaction", "of", "Rho", "with", "residues", "within", "the", "DH", "domain", "enhances", "the", "exchange", "of", "GDP", "for", "GTP", "and", "thus", "converts", "Rho", "into", "the", "biologically", "active", "form.", "Thus,", "the", "intracellular", "ratio", "of", "the", "GTP/GDP-bound", "forms", "of", "Rho", "proteins", "determines", "the", "activation", "of", "signal", "transduction", "pathways", "regulating", "the", "spatial", "and", "temporal", "reorganization", "of", "cytoskeletal", "architecture.", "[3]", "Members", "of", "the", "Rho", "subfamily", "of", "Ras-like", "monomeric", "GTPases,", "including", "Rho,", "Rac", "and", "Cdc42,", "are", "involved", "in", "a", "broad", "range", "of", "functions", "including", "gene", "transcription,", "cell", "cycle", "progression,", "cell", "polarity", "and", "most", "notably", "regulation", "of", "the", "actin", "cytoskeleton", "and", "cell", "morphology.", "[4]", "RhoGEF", "family", "is", "a", "widespread", "family", "found", "commonly", "in", "almost", "all", "organisms", "like", "Humans,", "Mouse,", "and", "Drosophila,", "C.", "elegans", "etc.", "In", "C.", "elegans", "this", "family", "consists", "of", "a", "large", "number", "of", "members", "and", "here", "the", "number", "of", "RhoGEF", "and", "RhoGAP", "regulators", "of", "Rho", "GTPases", "significantly", "exceeds", "the", "number", "of", "Rho", "family", "GTPases.", "These", "regulators", "likely", "provide", "the", "signaling", "specificity", "and", "spatial-temporal", "regulation", "required", "by", "the", "broadly", "expressed", "and", "functionally", "ISSN", "0973-2063", "Bioinformation", "2(2):", "43-49", "(2007)", "43", "important", "Rho", "family", "GTPases.", "Alternative", "splicing", "has", "recently", "emerged", "as", "a", "major", "mechanism", "of", "generating", "protein", "diversity", "in", "higher", "eukaryotes", "including", "nematodes", "Caenorhabditis", "elegans.", "[5,", "6,", "7]", "Several", "cases", "of", "alternative", "RNA", "splicing", "have", "been", "found", "in", "various", "RhoGEF", "domain", "containing", "and", "Rho", "related", "proteins", "in", "various", "organisms", "[8,", "9]", "and", "even", "in", "other", "RhoGEF", "domain", "containing", "genes", "of", "C.", "elegans.", "[10]", "Currently,", "most", "efficient", "methods", "use", "expressed", "sequence", "tags", "or", "microarray", "analysis", "for", "efficient", "detection", "of", "alternative", "splicing.", "[11-14]", "However,", "it", "is", "difficult", "to", "detect", "all", "alternative", "splice", "events", "with", "them", "because", "of", "their", "inherent", "limitations", "as", "discussed.", "[15]", "Recently,", "we", "successfully", "demonstrated", "identification", "of", "novel", "transcripts", "using", "a", "bioinformatics", "methodology", "involving", "both", "computational", "and", "experimental", "analysis", "in", "C.", "elegans.", "[15]", "Genefinder", "prediction", "by", "the", "C.", "elegans", "sequencing", "consortium", "of", "genomic", "sequence", "of", "Y95B8A.12", "has", "reported", "two", "spliced", "transcripts", "Y95B8A.12a", "and", "Y95B8A.12b", "that", "arise", "as", "a", "result", "of", "alternative", "splicing", "alternative", "splicing", "of", "pre-mRNA", "in", "the", "intronic", "region", "between", "exon", "2", "and", "exon", "3", "of", "Y95B8A.12.", "Detailed", "analysis", "of", "Y95B8A.12", "gene", "using", "a", "wide", "array", "of", "bioinformatics", "tools", "and", "programmes", "like", "gene/exon/ORF", "finding", "tools,", "BLAST", "analysis,", "sequence", "alignment", "programmes", "and", "many", "more;", "we", "predicted", "the", "existence", "of", "atleast", "four", "new", "Bioinformation,", "an", "open", "access", "forum", "©", "2007", "Biomedical", "Informatics", "Publishing", "Group" ]

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[ "BEHAVIORAL", "NEUROSCIENCE", "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "09", "February", "2012", "doi:", "10.3389/fnbeh.2012.00004", "Conflict", "processing", "in", "the", "rat", "brain:", "behavioral", "analysis", "and", "functional", "μPET", "imaging", "using", "[18F]fluorodeoxyglucose", "Christine", "Marx", "1*,", "Björn", "Lex", "2,", "Carsten", "Calaminus", "2,3,", "Wolfgang", "Hauber", "2,", "Heiko", "Backes", "1,", "Bernd", "Neumaier", "1,", "Günter", "Mies", "1,", "Rudolf", "Graf", "1", "and", "Heike", "Endepols", "1", "1", "Max", "Planck", "Institute", "for", "Neurological", "Research,", "Cologne,", "Germany", "2", "Department", "of", "Animal", "Physiology,", "Institute", "of", "Biology,", "University", "of", "Stuttgart,", "Stuttgart,", "Germany", "3", "Laboratory", "for", "Preclinical", "Imaging", "and", "Imaging", "Technology", "of", "the", "Werner", "Siemens-Foundation,", "Department", "of", "Preclinical", "Imaging", "and", "Radiopharmacy,", "University", "of", "Tübingen,", "Tübingen,", "Germany", "Edited", "by:", "Jeff", "Dalley,", "University", "of", "Cambridge,", "UK", "Reviewed", "by:", "Irini", "Skaliora,", "Biomedical", "Research", "Foundation", "of", "the", "Academy", "of", "Athens,", "Greece", "Paul", "Cumming,", "Ludwig-Maximilians", "University", "of", "Munich,", "Germany", "Daniele", "Caprioli,", "University", "of", "Cambridge,", "UK", "*Correspondence:", "Christine", "Marx,", "Max", "Planck", "Institute", "for", "Neurological", "Research,", "Gleueler", "Street", "50,", "50931", "Cologne,", "Germany.", "e-mail:", "christine.marx@nf.mpg.de", "Conflicts", "in", "spatial", "stimulus–response", "tasks", "occur", "when", "the", "task-relevant", "feature", "of", "a", "stimulus", "implies", "a", "response", "toward", "a", "certain", "location", "which", "does", "not", "match", "the", "location", "of", "stimulus", "presentation.", "This", "conflict", "leads", "to", "increased", "error", "rates", "and", "longer", "reaction", "times,", "which", "has", "been", "termed", "Simon", "effect.", "A", "model", "of", "dual", "route", "processing", "(automatic", "and", "intentional)", "of", "stimulus", "features", "has", "been", "proposed,", "predicting", "response", "conflicts", "if", "the", "two", "routes", "are", "incongruent.", "Although", "there", "is", "evidence", "that", "the", "prefrontal", "cortex,", "notably", "the", "anterior", "cingulate", "cortex", "(ACC),", "plays", "a", "crucial", "role", "in", "conflict", "processing,", "the", "neuronal", "basis", "of", "dual", "route", "architecture", "is", "still", "unknown.", "In", "this", "study,", "we", "pursue", "a", "novel", "approach", "using", "positron", "emission", "tomography", "(PET)", "to", "identify", "relevant", "brain", "areas", "in", "a", "rat", "model", "of", "an", "auditory", "Simon", "task,", "a", "neuropsychological", "interference", "task,", "which", "is", "com-", "monly", "used", "to", "study", "conflict", "processing", "in", "humans.", "For", "combination", "with", "PET", "we", "used", "the", "metabolic", "tracer", "[18F]fluorodeoxyglucose,", "which", "accumulates", "in", "metabolically", "active", "brain", "cells", "during", "the", "behavioral", "task.", "Brain", "areas", "involved", "in", "conflict", "processing", "are", "supposed", "to", "be", "activated", "when", "automatic", "and", "intentional", "route", "processing", "lead", "to", "different", "responses", "(dual", "route", "model).", "Analysis", "of", "PET", "data", "revealed", "specific", "activation", "patterns", "for", "different", "task", "settings", "applicable", "to", "the", "dual", "route", "model", "as", "established", "for", "response", "conflict", "pro-", "cessing.", "The", "rat", "motor", "cortex", "(M1)", "may", "be", "part", "of", "the", "automatic", "route", "or", "involved", "in", "its", "facilitation,", "while", "premotor", "(M2),", "prelimbic,", "and", "ACC", "seemed", "to", "be", "essential", "for", "inhibiting", "the", "incorrect,", "automatic", "response,", "indicating", "conflict", "monitoring", "functions.", "Our", "findings", "and", "the", "remarkable", "similarities", "to", "the", "pattern", "of", "activated", "regions", "reported", "during", "conflict", "processing", "in", "humans", "demonstrate", "that", "our", "rodent", "model", "opens", "novel", "opportunities", "to", "investigate", "the", "anatomical", "basis", "of", "conflict", "processing", "and", "dual", "route", "architecture.", "Keywords:", "prefrontal", "cortex,", "rodent", "model,", "cognitive", "conflict,", "Simon", "task", "INTRODUCTION", "The", "limits", "of", "cognitive", "capacity", "are", "especially", "evident", "during", "attempts", "to", "perform", "simultaneously", "several", "tasks,", "such", "as", "speak-", "ing", "and", "typing.", "This", "leads", "to", "conflicts", "in", "the", "cognitive", "system", "and", "hence,", "to", "slower", "activity", "and", "in", "the", "worst", "case,", "to", "action", "slips,", "as", "typing", "errors.", "An", "established", "method", "to", "analyze", "such", "conflicts", "is", "the", "so", "called", "Simon", "task", "(Simon", "et", "al.,", "1970).", "For", "example,", "when", "a", "stimulus", "indicates", "that", "a", "left", "button", "press", "is", "required,", "a", "response", "conflict", "arises", "if", "the", "stimulus", "is", "presented", "on", "the", "right-hand", "side.", "The", "Simon", "effect", "is", "a", "neuropsychological", "interference", "effect", "in", "which", "reaction", "times", "(RTs)", "are", "longer", "and", "errors", "more", "frequent", "when", "spatial", "features", "of", "the", "stimulus", "(although", "task-irrelevant)", "are", "inconsistent", "with", "spatial", "attributes", "of", "the", "response", "(Simon", "et", "al.,", "1970).", "Contemporary", "models", "assume", "that", "the", "Simon", "effect", "reflects", "basic", "cognitive", "mechanisms", "in", "which", "sensorimotor", "pro-", "cessing", "occurs", "via", "two", "different", "channels", "(De", "Jong", 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[ "Int", "J", "Colorectal", "Dis", "(2008)", "23:305–317", "DOI", "10.1007/s00384-007-0396-6", "ORIGINAL", "ARTICLE", "NF-κB-dependent", "synergistic", "regulation", "of", "CXCL10", "gene", "expression", "by", "IL-1β", "and", "IFN-γ", "in", "human", "intestinal", "epithelial", "cell", "lines", "Sunil", "Yeruva", "&", "Giuliano", "Ramadori", "&", "Dirk", "Raddatz", "Accepted:", "17", "October", "2007", "/", "Published", "online:", "28", "November", "2007", "#", "Springer-Verlag", "2007", "Abstract", "Background", "and", "aims", "Little", "is", "known", "about", "the", "intestinal", "epithelial", "expression", "and", "secretion", "of", "CXCL10", "(IP-10),", "a", "chemokine", "involved", "in", "recruiting", "T", "cells", "and", "monocytes.", "We", "aimed", "to", "study", "CXCL10", "gene", "expression", "and", "regula-", "tion", "by", "the", "pro-inflammatory", "cytokines", "interleukin", "(IL)-1β,", "interferon", "(IFN)-γ", "and", "tumour", "necrosis", "factor", "(TNF)-α", "in", "intestinal", "epithelial", "cell", "lines.", "Materials", "and", "methods", "CXCL10", "expression", "and", "secretion", "kinetics", "were", "assessed", "in", "Caco-2,", "HT-29", "and", "DLD1", "human", "colon", "epithelial", "cells,", "treated", "with", "IL-1β,", "TNF-α,", "IFN-γ", "alone", "or", "in", "combination", "with", "each", "other", "by", "real-time", "polymerase", "chain", "reaction", "(PCR),", "Northern", "blotting", "and", "enzyme-linked", "immunoabsorbent", "assay", "(ELISA).", "Transient", "transfections", "with", "TGL-IP10", "(CXCL10", "promoter)", "and", "TGL-IP10-κB2", "mutant", "promoter", "and", "gelshifts", "and", "super-", "shifts", "for", "nuclear", "factor", "(NF)-κB", "were", "also", "performed.", "S.", "Yeruva", ":", "G.", "Ramadori", ":", "D.", "Raddatz", "Centre", "for", "Internal", "Medicine,", "Department", "of", "Gastroenterology", "and", "Endocrinology,", "University", "of", "Göttingen,", "Goettingen,", "Germany", "D.", "Raddatz", "(*)", "Department", "of", "Gastroenterology", "and", "Endocrinology,", "University", "clinic", "of", "Göttingen,", "Robert", "Koch", "Strasse", "40,", "37075", "Goettingen,", "Germany", "e-mail:", "draddat@gwdg.de", "Present", "address:", "S.", "Yeruva", "Department", "of", "Gastroenterology,", "Hepatology", "and", "Endocrinology,", "Hannover", "Medical", "School,", "Carl-Neuberg", "Strasse-1,", "30625", "Hannover,", "Germany", "Results", "Real-time", "PCRs", "and", "ELISA", "experiments", "revealed", "that", "IL-1β", "was", "the", "strongest", "and", "earliest", "inducer", "of", "CXCL10", "messenger", "ribonucleic", "acid", "(mRNA)", "expression", "and", "protein", "secretion", "in", "Caco-2", "cell", "line,", "whereas", "INF-γ", "had", "a", "delayed", "kinetics.", "There", "was", "a", "strong", "synergistic", "effect", "of", "either", "TNF-α", "or", "IL-1β", "with", "IFN-γ", "both", "on", "CXCL10", "mRNA", "expression", "and", "protein", "secretion", "in", "all", "three", "cell", "lines.", "Real-time", "PCR", "and", "ELISA", "experiments", "using", "a", "specific", "NF-", "κB", "inhibitor", "and", "transfection", "experiments", "with", "a", "NF-κB-", "binding", "defective", "CXCL10", "promoter", "construct", "revealed", "that", "the", "induction", "of", "CXCL10", "by", "IL-1β", "and", "its", "synergism", "with", "IFN-γ", "is", "NF-κB", "dependent.", "Conclusion", "These", "data", "demonstrate", "that", "in", "colonic", "epithe-", "lial", "cells,", "depending", "on", "the", "cellular", "context", "and", "utilizing", "the", "NF-κB", "pathway,", "IL-1β", "alone", "and/or", "in", "synergism", "with", "IFN-γ", "may", "play", "a", "major", "role", "in", "the", "induction", "of", "CXCL10.", "Keywords", "Intestinal", "epithelial", "cells", ".", "Nuclear", "factor", "kappa", "B", ".", "Inflammatory", "bowel", "disease", ".", "Cytokines", "and", "chemokines", ".", "Colon", "cancer", "Introduction", "Intestinal", "epithelial", "cells", "(IECs)", "form", "the", "first", "immunologic", "barrier", "of", "the", "organism", "while", "the", "villus", "surface", "is", "continuously", "in", "contact", "with", "various", "agents.", "IEC", "gene", "expression", "is", "tightly", "regulated", "to", "induce", "appropriate", "responses", "to", "pathogens", "and", "to", "avoid", "deleterious", "reactions", "to", "microbial", "flora.", "When", "stimulated", "with", "pro-inflammatory", "cytokines", "or", "infected", "with", "microbial", "pathogens,", "IECs", "may", "secrete", "chemokines,", "a", "set", "of", "low-molecular", "weight", "cyto-", "kines,", "directing", "migration", "and", "activation", "of", "leucocytes,", "which", "play", "a", "major", "role", "in", "the", "perpetuation", "of", "inflammatory", "processes", "[1–5].", "The", "final", "composition", "of", "leucocytes" ]

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[ "Cough", "Commentary", "Defining", "the", "relationship", "between", "gastroesophageal", "reflux", "and", "cough:", "probabilities,", "possibilities", "and", "limitations", "Matthew", "M", "Eastburn1,2,", "Peter", "H", "Katelaris3", "and", "Anne", "B", "Chang*1,4", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Respiratory", "Medicine,", "Royal", "Children's", "Hospital,", "Brisbane,", "Australia,", "2School", "of", "Information", "Technology", "and", "Electrical", "Engineering,", "University", "of", "Queensland,", "St", "Lucia,", "Queensland,", "Australia,", "3Department", "of", "Gastroenterology,", "University", "of", "Sydney,", "Concord", "Hospital,", "Sydney,", "Australia", "and", "4Child", "Health", "Division,", "Menzies", "School", "of", "Health", "Research,", "Darwin,", "Northern", "Territory,", "Australia", "Email:", "Matthew", "M", "Eastburn", "-", "matt.eastburn@brainlab.com;", "Peter", "H", "Katelaris", "-", "pkatelar@mail.usyd.edu.au;", "Anne", "B", "Chang*", "-", "annechang@ausdoctors.net", "*", "Corresponding", "author", "Published:", "20", "March", "2007", "Cough", "2007,", "3:4", "doi:10.1186/1745-9974-3-4", "This", "article", "is", "available", "from:", "http://www.coughjournal.com/content/3/1/4", "Received:", "30", "January", "2007", "Accepted:", "20", "March", "2007", "©", "2007", "Eastburn", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "The", "common", "co-existence", "of", "cough", "and", "gastroesophageal", "reflux", "disease", "(GORD)", "is", "well", "established.", "However,", "ascertaining", "cause", "and", "effect", "is", "more", "difficult", "for", "many", "reasons", "that", "include", "occurrence", "by", "chance", "of", "two", "common", "symptoms,", "the", "changing", "definition", "of", "GORD,", "equipment", "limitations", "and", "the", "lack", "of", "randomised", "controlled", "trials.", "Given", "these", "difficulties,", "it", "is", "not", "surprising", "that", "there", "is", "disparity", "of", "opinion", "between", "respiratory", "and", "gastroenterology", "society", "guidelines", "on", "the", "link", "between", "GORD", "and", "chronic", "cough.", "This", "commentary", "explores", "of", "these", "issues.", "Background", "The", "first", "guideline", "on", "the", "management", "of", "cough", "champi-", "oned", "by", "Irwin", "[1]", "made", "a", "significant", "positive", "impact.", "Not", "surprisingly", "other", "guidelines", "on", "chronic", "cough", "[2-5]", "have", "since", "been", "published.", "American", "[2],", "European", "[3]", "and", "British", "[5]", "respiratory", "guidelines", "for", "the", "management", "of", "chronic", "unexplained", "cough", "in", "adults", "advocate", "empirical", "treatment", "of", "gastroesophageal", "reflux", "disease", "(GORD)", "with", "a", "variety", "of", "medications", "including", "proton", "pump", "inhibitors", "(PPIs).", "In", "contrast,", "guidelines", "from", "some", "national", "gastroenterological", "societies", "are", "less", "definitive", "about", "the", "association", "between", "cough", "and", "GORD", "[6-9]", "Paediatric", "cough", "guidelines", "do", "not", "favour", "the", "empirical", "approach", "in", "adults", "because", "GORD", "as", "a", "cause", "of", "isolated", "cough", "is", "rare", "in", "children", "[10,11].", "Is", "there", "evidence", "for", "a", "true", "difference", "or", "do", "these", "differences", "exist", "because", "opin-", "ion", "leaders", "in", "their", "respective", "fields", "have", "different", "views?", "In", "this", "commentary,", "important", "limitations", "in", "understand-", "ing", "the", "association", "between", "cough", "and", "GORD", "are", "explored.", "That", "cough", "and", "GORD", "commonly", "coexist", "is", "indisputable", "in", "both", "children", "[12]", "and", "adults", "[13].", "The", "questions", "of", "whether", "this", "is", "'cause", "and", "effect'", "[14],", "'whether", "GORD", "causes", "cough", "or", "vice", "versa'", "[15]", "and", "'how", "commonly", "can", "the", "symptom", "of", "cough", "be", "attributed", "to", "GORD'", "remain", "controversial", "[9,16].", "Nevertheless", "the", "problem", "is", "real;", "in", "the", "community", "the", "burden", "of", "cough", "and", "GORD,", "in", "isola-", "tion", "or", "in", "combination,", "is", "high.", "Chronic", "cough", "is", "associ-", "ated", "with", "significant", "morbidity", "[17]", "and", "the", "economic", "cost", "in", "terms", "of", "medications", "alone,", "is", "billions", "of", "dollars", "[18].", "Empirical", "acid", "antisecretory", "treatment", "of", "cough", "in", "adults", "adds", "to", "this", "cost.", "In", "Australia", "alone,", "where", "the", "costs", "of", "medications", "are", "heavily", "subsided", "by", "the", "government,", "three", "PPIs", "are", "in", "the", "top", "10", "drugs", "by", "cost", "[19].", "In", "2006", "these", "3", "PPIs", "alone", "costs", "the", "Australian", "tax", "payers", "almost", "A$42.5", "million", "[19].", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Harm", "Reduction", "Journal", "Research", "Seroprevalence", "of", "select", "bloodborne", "pathogens", "and", "associated", "risk", "behaviors", "among", "injection", "drug", "users", "in", "the", "Paso", "del", "Norte", "region", "of", "the", "United", "States", "–", "Mexico", "border", "Joan", "P", "Baumbach*1,", "Lily", "N", "Foster1,", "Mark", "Mueller1,", "Michelle", "Firestone", "Cruz2,", "Sonia", "Arbona3,", "Sharon", "Melville3,", "Rebeca", "Ramos4", "and", "Steffanie", "A", "Strathdee5", "BioMed", "Central", "Open", "Access", "Address:", "1New", "Mexico", "Department", "of", "Health,", "Santa", "Fe,", "NM,", "USA,", "2Centre", "for", "Addiction", "and", "Mental", "Health,", "Toronto,", "ON,", "Canada,", "3Texas", "Department", "of", "State", "Health", "Services,", "Austin,", "TX,", "USA,", "4United", "States", "–", "Mexico", "Border", "Health", "Association,", "El", "Paso,", "TX,", "USA", "and", "5University", "of", "California,", "San", "Diego,", "CA,", "USA", "Email:", "Joan", "P", "Baumbach*", "-", "joan.baumbach@state.nm.us;", "Lily", "N", "Foster", "-", "lily.foster@state.nm.us;", "Mark", "Mueller", "-", "mark.mueller@state.nm.us;", "Michelle", "Firestone", "Cruz", "-", "michelle.firestone@utoronto.ca;", "Sonia", "Arbona", "-", "sonia.arbona@dshs.state.tx.us;", "Sharon", "Melville", "-", "sharon.melville@dshs.tx.state.us;", "Rebeca", "Ramos", "-", "rebeca@utep.edu;", "Steffanie", "A", "Strathdee", "-", "sstrathdee@ucsd.edu", "*", "Corresponding", "author", "Published:", "16", "November", "2008", "Harm", "Reduction", "Journal", "2008,", "5:33", "doi:10.1186/1477-7517-5-33", "This", "article", "is", "available", "from:", "http://www.harmreductionjournal.com/content/5/1/33", "Received:", "13", "March", "2008", "Accepted:", "16", "November", "2008", "©", "2008", "Baumbach", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "region", "situated", "where", "the", "borders", "of", "Mexico,", "Texas", "and", "New", "Mexico", "meet", "is", "known", "as", "'Paso", "del", "Norte'.", "The", "Paso", "del", "Norte", "Collaborative", "was", "formed", "to", "study", "the", "seroprevalence", "of", "select", "pathogens", "and", "associated", "risk", "behaviors", "among", "injection", "drug", "users", "(IDUs)", "in", "the", "region.", "Methods:", "Respondent-driven", "sampling", "(RDS)", "was", "used:", "459", "IDU", "participants", "included", "204", "from", "Mexico;", "155", "from", "Texas;", "and", "100", "from", "New", "Mexico.", "Each", "of", "the", "three", "sites", "used", "a", "standardized", "questionnaire", "that", "was", "verbally", "administered", "and", "testing", "was", "performed", "for", "select", "bloodborne", "infections.", "Results:", "Participants", "were", "mostly", "male", "(87.4%)", "and", "Hispanic/Latino", "(84.7%)", "whose", "median", "age", "was", "38.", "In", "Mexico,", "Texas", "and", "New", "Mexico,", "respectively:", "hepatitis", "B", "virus", "(HBV)", "was", "seen", "in", "88.3%,", "48.6%", "and", "59.6%", "of", "participants;", "hepatitis", "C", "virus", "(HCV)", "in", "98.7%,", "76.4%", "and", "80.0%;", "human", "immunodeficiency", "virus", "(HIV)", "in", "2.1%,", "10.0%", "and", "1.0%;", "and", "syphilis", "in", "4.0%,", "9.9%", "and", "3.0%.", "Heroin", "was", "the", "drug", "injected", "most", "often.", "More", "IDUs", "in", "New", "Mexico", "were", "aware", "of", "and", "used", "needle", "exchange", "programs", "compared", "with", "Texas", "and", "Mexico.", "Conclusion:", "There", "was", "mixed", "success", "using", "RDS:", "it", "was", "more", "successfully", "applied", "after", "establishing", "good", "working", "relationships", "with", "IDU", "populations.", "Study", "findings", "included", "similarities", "and", "distinctions", "between", "the", "three", "sites", "that", "will", "be", "used", "to", "inform", "prevention", "interventions.", "Introduction", "The", "'Paso", "del", "Norte'", "region", "(See", "Figure", "1)", "straddles", "the", "midpoint", "of", "the", "U.S-Mexico", "border.", "It", "contains", "Ciudad", "Juárez", "in", "Chihuahua,", "Mexico,", "El", "Paso,", "Texas", "and", "Doña", "Ana", "County,", "New", "Mexico.", "It", "is", "a", "suitable", "site", "for", "the", "study", "of", "risk", "behaviors", "associated", "with", "injection", "drug", "use", "because:", "a)", "many", "people", "there", "lead", "lives", "on", "both", "sides", "of", "the", "border;", "b)", "there", "are", "known", "injection", "drug", "use", "(IDU)", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "CytoJournal", "Editorial", "Thank", "you", "reviewers-", "CytoJournal", "2006", "Vinod", "B", "Shidham*1", "and", "Barbara", "F", "Atkinson2", "Address:", "1Dept", "of", "Pathology,", "Medical", "College", "of", "Wisconsin,", "Milwaukee,", "WI,", "USA", "and", "2Exective", "Vice", "Chancellor", "&", "Executive", "Dean,", "University", "of", "Kansas", "School", "of", "Medicine,", "Kansas", "City,", "KS,", "USA", "Email:", "Vinod", "B", "Shidham*", "-", "vshidham@mcw.edu;", "Barbara", "F", "Atkinson", "-", "batkinson@kumc.edu", "*", "Corresponding", "author", "Published:", "03", "February", "2006", "CytoJournal", "2006,", "3:2", "doi:10.1186/1742-6413-3-2", "This", "article", "is", "available", "from:", "http://www.cytojournal.com/content/3/1/2", "Received:", "26", "January", "2006", "Accepted:", "03", "February", "2006", "©", "2006", "Shidham", "and", "Atkinson;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "The", "Editorial", "Board", "of", "CytoJournal", "devotes", "significant", "efforts,", "time,", "and", "resources", "to", "review", "numerous", "manuscripts.", "As", "it", "is", "impossible", "to", "include", "all", "the", "experts", "on", "the", "editorial", "board,", "there", "is", "always", "a", "need", "for", "additional", "peers", "who", "are", "requested", "to", "join", "periodically", "to", "act", "as", "'academic", "editors'", "and", "reviewers.", "We", "take", "this", "opportunity", "to", "thank", "all", "the", "reviewers", "and", "academic", "editors", "who", "offered", "their", "time", "and", "efforts", "by", "participating", "in", "peer-review", "process", "for", "CytoJournal", "manuscripts.", "We", "request", "their", "continued", "enthusiasm", "to", "support", "this", "important", "academic", "exercise.", "BioMed", "Central", "Open", "Access", "According", "to", "the", "'close", "review'", "policy", "of", "CytoJournal,", "the", "peer-reviewers", "are", "not", "identified", "in", "the", "individual", "manu-", "scripts", "and", "articles.", "But", "the", "'academic", "editors',", "who", "con-", "duct", "and", "complete", "the", "peer-review", "process", "by", "appointing", "reviewers", "are", "acknowledged", "in", "the", "articles", "[1,1-9].", "How-", "ever,", "all", "the", "submitted", "manuscripts", "are", "not", "accepted", "for", "publication.", "The", "academic", "editors,", "reviewing", "such", "manu-", "scripts,", "can", "not", "be", "thanked", "through", "the", "published", "articles.", "As", "a", "token", "of", "appreciation", "and", "thanks,", "CytoJournal", "would", "publish", "periodically", "the", "list", "of", "all", "the", "academic", "editors", "and", "reviewers", "involved", "in", "the", "peer-review", "process", "of", "all", "the", "manuscripts", "submitted", "to", "CytoJournal", "irrespective", "of", "their", "publication", "status.", "On", "behalf", "of", "CytoJournal's", "editorial", "body", "and", "Cytopa-", "thology-Foundation", "Inc,", "we", "take", "this", "opportunity", "to", "spe-", "cifically", "thank", "all", "reviewers", "and", "academic", "editors", "listed", "in", "the", "Table", "1.", "Their", "time", "and", "efforts", "for", "reviewing", "the", "man-", "uscript", "and", "improving", "the", "quality", "of", "the", "published", "articles", "in", "CytoJournal", "[10-26]", "is", "commendable.", "The", "quality", "of", "peer-review", "is", "extremely", "important", "to", "continue", "and", "enhance", "the", "high", "standards", "of", "CytoJournal.", "We", "also", "thank", "all", "the", "authors", "that", "submitted", "the", "manu-", "scripts", "to", "CytoJournal", "and", "supported", "the", "'open", "access'", "ini-", "tiative", "in", "cytopathology.", "'Open", "access'", "extends", "numerous", "benefits", "to", "the", "authors", "including", "the", "retention", "of", "their", "copyrights", "to", "the", "published", "material", "[27].", "We", "invite", "all", "the", "experts", "in", "cytopathology", "and", "related", "areas", "to", "join", "the", "ever", "increasing", "demand", "of", "good", "review-", "ers.", "High", "standard", "of", "peer-review", "process", "of", "CytoJournal", "is", "the", "topmost", "agenda", "at", "periodic", "'reviewer's", "retreats'.", "Existing", "editorial", "board", "members", "and", "potential", "core", "reviewers", "could", "participate", "at", "such", "retreats", "[28].", "It", "is", "a", "great", "opportunity", "to", "be", "involved", "actively", "for", "the", "benefits", "of", "'open", "access'", "initiative", "in", "cytopathology.", "Open", "access", "offers", "limitless", "potential", "advantages", "to", "our", "profession", "and", "general", "public", "by", "providing", "free", "access", "to", "the", "scientific", "lit-", "erature", "generated", "by", "us", "as", "academia", "by", "collective", "pro", "bono", "hard", "work.", "To", "join", "as", "a", "core", "reviewer", "of", "CytoJournal,", "please", "e-mail", "the", "details", "by", "copy", "pasting", "the", "brief", "form", "(Table", "2)", "in", "the", "body", "of", "your", "e-mail", "and", "also", "attaching", "a", "copy", "of", "your", "CV", "to", "cytojournal@mcw.edu.", "A", "list", "of", "all", "the", "core", "reviewers", "of", "CytoJournal", "is", "planned", "to", "be", "displayed", "on", "the", "web", "page", "in", "the", "future.", "Page", "1", "of", "3", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Aberegg", "et", "al.", "Critical", "Care", "2010,", "14:R77", "http://ccforum.com/content/14/2/R77", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "RDeseealrtcha", "inflation:", "a", "bias", "in", "the", "design", "of", "randomized", "controlled", "trials", "in", "critical", "care", "medicine", "Scott", "K", "Aberegg*1,", "D", "Roxanne", "Richards2", "and", "James", "M", "O'Brien3", "Abstract", "Introduction:", "Mortality", "is", "the", "most", "widely", "accepted", "outcome", "measure", "in", "randomized", "controlled", "trials", "of", "therapies", "for", "critically", "ill", "adults,", "but", "most", "of", "these", "trials", "fail", "to", "show", "a", "statistically", "significant", "mortality", "benefit.", "The", "reasons", "for", "this", "are", "unknown.", "Methods:", "We", "searched", "five", "high", "impact", "journals", "(Annals", "of", "Internal", "Medicine,", "British", "Medical", "Journal,", "JAMA,", "The", "Lancet,", "New", "England", "Journal", "of", "Medicine)", "for", "randomized", "controlled", "trials", "comparing", "mortality", "of", "therapies", "for", "critically", "ill", "adults", "over", "a", "ten", "year", "period.", "We", "abstracted", "data", "on", "the", "statistical", "design", "and", "results", "of", "these", "trials", "to", "compare", "the", "predicted", "delta", "(delta;", "the", "effect", "size", "of", "the", "therapy", "compared", "to", "control", "expressed", "as", "an", "absolute", "mortality", "reduction)", "to", "the", "observed", "delta", "to", "determine", "if", "there", "is", "a", "systematic", "overestimation", "of", "predicted", "delta", "that", "might", "explain", "the", "high", "prevalence", "of", "negative", "results", "in", "these", "trials.", "Results:", "We", "found", "38", "trials", "meeting", "our", "inclusion", "criteria.", "Only", "5/38", "(13.2%)", "of", "the", "trials", "provided", "justification", "for", "the", "predicted", "delta.", "The", "mean", "predicted", "delta", "among", "the", "38", "trials", "was", "10.1%", "and", "the", "mean", "observed", "delta", "was", "1.4%", "(P", "<", "0.0001),", "resulting", "in", "a", "delta-gap", "of", "8.7%.", "In", "only", "2/38", "(5.3%)", "of", "the", "trials", "did", "the", "observed", "delta", "exceed", "the", "predicted", "delta", "and", "only", "7/38", "(18.4%)", "of", "the", "trials", "demonstrated", "statistically", "significant", "results", "in", "the", "hypothesized", "direction;", "these", "trials", "had", "smaller", "delta-gaps", "than", "the", "remainder", "of", "the", "trials", "(delta-gap", "0.9%", "versus", "10.5%;", "P", "<", "0.0001).", "For", "trials", "showing", "non-significant", "trends", "toward", "benefit", "greater", "than", "3%,", "large", "increases", "in", "sample", "size", "(380%", "-", "1100%)", "would", "be", "required", "if", "repeat", "trials", "use", "the", "observed", "delta", "from", "the", "index", "trial", "as", "the", "predicted", "delta", "for", "a", "follow-up", "study.", "Conclusions:", "Investigators", "of", "therapies", "for", "critical", "illness", "systematically", "overestimate", "treatment", "effect", "size", "(delta)", "during", "the", "design", "of", "randomized", "controlled", "trials.", "This", "bias,", "which", "we", "refer", "to", "as", "\"delta", "inflation\",", "is", "a", "potential", "reason", "that", "these", "trials", "have", "a", "high", "rate", "of", "negative", "results.", "“Absence", "of", "evidence", "is", "not", "evidence", "of", "absence.”", "Introduction", "Mortality", "has", "become", "the", "standard", "outcome", "measure", "in", "trials", "of", "therapies", "in", "critically", "ill", "adults", "because", "it", "obviates", "debate", "about", "clinical", "relevance", "and", "concerns", "of", "ascertain-", "ment", "bias.", "However,", "it", "has", "recently", "been", "noted", "that", "the", "majority", "of", "these", "trials", "fail", "to", "demonstrate", "efficacy", "[1]", "and", "several", "therapies", "that", "appeared", "promising", "did", "not", "dem-", "onstrate", "efficacy", "on", "repeated", "study", "[2-7].", "The", "high", "rate", "of", "negative", "results", "in", "these", "trials", "could", "be", "explained", "by", "sev-", "eral", "possibilities", "including", "true", "lack", "of", "efficacy", "(the", "null", "hypothesis", "is", "true),", "type", "II", "statistical", "errors", "in", "trials", "with", "*", "Correspondence:", "scottaberegg@gmail.com", "1", "Department", "of", "Critical", "Care,", "Jordan", "Valley", "Medical", "Center,", "3580", "West", "9000", "South,", "West", "Jordan,", "Utah,", "84088,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "adequate", "power,", "and", "methodological", "problems", "in", "study", "design", "leading", "to", "inadequate", "power", "and", "sample", "size", "[8].", "Several", "parameters", "must", "be", "chosen", "by", "investigators", "in", "the", "design", "of", "a", "trial", "of", "mortality", "in", "order", "to", "determine", "the", "required", "sample", "size,", "including", "the", "significance", "level", "required", "for", "rejection", "of", "the", "null", "hypothesis;", "power;", "the", "predicted", "mortality", "rate", "in", "the", "placebo", "arm;", "and", "the", "pre-", "dicted", "effect", "size", "(delta).", "In", "contrast", "to", "significance", "level", "and", "power,", "which", "are", "usually", "set", "by", "convention", "at", "0.05", "and", "90%,", "respectively,", "predictions", "about", "the", "placebo", "mor-", "tality", "rate", "must", "be", "guided", "by", "preliminary", "data", "(if", "avail-", "able)", "or", "guesswork.", "Likewise,", "predictions", "of", "delta", "are", "either", "based", "on", "existing", "data", "or", "are", "guided", "by", "biological", "plausibility", "or", "a", "minimal", "clinically", "important", "difference", "(MCID)", "[9,10].", "Using", "these", "four", "variables", "(significance", "level,", "power,", "baseline", "mortality", "rate,", "and", "delta)", "sample", "size", "required", "for", "the", "trial", "can", "be", "calculated.", "©", "2010", "Aberegg", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "BioMed", "Central", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "International", "Journal", "of", "Behavioral", "Nutrition", "and", "Physical", "Activity", "Research", "Association", "between", "obesity,", "quality", "of", "life,", "physical", "activity", "and", "health", "service", "utilization", "in", "primary", "care", "patients", "with", "osteoarthritis", "Thomas", "Rosemann*1,2,", "Richard", "Grol3,", "Katja", "Herman1,", "Michel", "Wensing3", "and", "Joachim", "Szecsenyi1", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "General", "Practice,", "University", "of", "Zürich,", "Rämistr.100,", "8001", "Zürich,", "Switzerland,", "2Department", "of", "General", "Practice", "and", "Health", "Services", "Research,", "University", "Hospital", "Heidelberg,", "Voßstr.", "2,", "69115", "Heidelberg,", "Germany", "and", "3Radboud", "University", "Nijmegen", "Medical", "Centre,", "6500", "HB", "Nijmegen,", "The", "Netherlands", "Email:", "Thomas", "Rosemann*", "-", "thomas.rosemann@med.uni-heidelberg.de;", "Richard", "Grol", "-", "richard.grol@kwazo.umcn.nl;", "Katja", "Herman", "-", "katja.hermann@med.uni-heidelberg.de;", "Michel", "Wensing", "-", "michel.wensing@uni-heidelberg.de;", "Joachim", "Szecsenyi", "-", "joachim.szecsenyi@med.uni-heidelberg.de", "*", "Corresponding", "author", "Published:", "28", "January", "2008", "Received:", "28", "June", "2007", "International", "Journal", "of", "Behavioral", "Nutrition", "and", "Physical", "Activity", "2008,", "5:4", "doi:10.1186/1479-", "Accepted:", "28", "January", "2008", "5868-5-4", "This", "article", "is", "available", "from:", "http://www.ijbnpa.org/content/5/1/4", "©", "2008", "Rosemann", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Objective:", "To", "assess", "the", "association", "of", "obesity", "with", "quality", "of", "life,", "health", "service", "utilization", "and", "physical", "activity", "in", "a", "large", "sample", "of", "primary", "care", "patients", "with", "osteoarthritis", "(OA).", "Methods:", "Data", "were", "retrieved", "from", "the", "PraxArt", "project,", "representing", "a", "cohort", "of", "1021", "primary", "care", "patients", "with", "OA.", "In", "978", "patients,", "height", "and", "weight", "were", "measured", "and", "the", "Body", "Mass", "Index", "(BMI)", "was", "calculated.", "The", "AIMS2-SF", "was", "used", "to", "assess", "quality", "of", "life", "(QoL).", "Data", "about", "health", "service", "utilization", "(HSU)", "were", "retrieved", "by", "means", "of", "patients'", "medical", "files.", "Concomitant", "depression", "was", "assessed", "by", "means", "of", "the", "Patient", "Health", "Questionnaire", "(PHQ-9).", "Patients", "were", "grouped", "into", "normal", "weight,", "overweight", "and", "obese", "according", "to", "the", "definition", "of", "the", "WHO", "and", "compared", "by", "means", "of", "analysis", "of", "covariance", "(ANCOVA).", "Results:", "Obese", "and", "overweight", "persons", "achieved", "significantly", "higher", "scores", "on", "the", "AIMS2-SF", "lower", "body", "scale,", "the", "symptom,", "the", "affect", "and", "the", "work", "scale,", "indicating", "an", "increased", "burden", "by", "OA.", "The", "PHQ-9", "score", "increased", "significantly", "over", "the", "three", "weight-groups,", "indicating", "a", "positive", "association", "of", "BMI", "and", "depression.", "With", "increasing", "BMI,", "the", "number", "of", "comorbidities", "increased", "and", "physical", "activity", "decreased", "significantly.", "After", "controlling", "for", "covariates,", "contacts", "to", "orthopaedics", "and", "performed", "x-rays", "remained", "significantly", "higher", "in", "obese", "patients,", "but", "not", "contacts", "to", "general", "practitioners.", "Conclusion:", "The", "results", "display", "a", "strong", "association", "of", "QoL", "and", "BMI,", "resulting", "in", "increased", "use", "of", "the", "health", "care", "system.", "Thus,", "the", "study", "emphasizes", "the", "need", "for", "appropriate", "approaches", "in", "primary", "care", "to", "break", "the", "vicious", "circle", "of", "overweight,", "depression,", "decreasing", "physical", "inactivity", "and", "decreasing", "QoL.", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Elamin", "and", "de", "Buyl", "Journal", "of", "Medical", "Case", "Reports", "2010,", "4:349", "http://www.jmedicalcasereports.com/content/4/1/349", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "JOURNAL", "OF", "MEDICAL", "CASE", "REPORTS", "Open", "Access", "A", "novel", "mutation", "in", "the", "calcium-sensing", "receptor", "gene", "in", "an", "Irish", "pedigree", "showing", "familial", "hypocalciuric", "hypercalcemia:", "a", "case", "report", "Wael", "F", "Elamin1,2*,", "Olivier", "de", "Buyl1", "Abstract", "Introduction:", "Familial", "hypocalciuric", "hypercalcemia", "is", "a", "rare", "autosomal", "dominant", "disorder", "characterized", "by", "asymptomatic", "and", "non-progressive", "hypercalcemia", "due", "to", "mutations", "of", "the", "calcium-sensing", "receptor", "gene.", "Disorders", "of", "calcium", "metabolism", "are", "very", "common", "in", "the", "elderly,", "and", "they", "can", "coexist", "with", "familial", "hypocalciuric", "hypercalcemia", "in", "affected", "families.", "Case", "presentation:", "We", "describe", "an", "Irish", "family", "with", "hypercalcemia", "and", "hypocalciuria.", "The", "proband,", "an", "80-year-old", "Irish", "woman,", "presented", "with", "hypercalcemia,", "relative", "hypocalciuria,", "and", "an", "elevated", "parathormone", "level.", "She", "also", "had", "chronic", "kidney", "disease", "stage", "3", "and", "vitamin", "D", "deficiency.", "Two", "of", "her", "sons", "were", "also", "found", "to", "be", "hypercalcemic", "and", "hypocalciuric.", "DNA", "sequencing", "identified", "a", "novel", "missense", "inactivating", "mutation", "in", "the", "calcium", "sensing-receptor", "gene", "of", "the", "proband", "and", "her", "two", "hypercalcemic", "sons.", "Conclusion:", "Familial", "hypocalciuric", "hypercalcemia", "due", "to", "a", "novel", "mutation", "in", "the", "calcium-sensing", "receptor", "gene", "was", "diagnosed", "in", "the", "proband", "and", "her", "two", "sons.", "Disorders", "of", "calcium", "metabolism", "can", "be", "multifarious", "in", "the", "elderly.", "We", "suggest", "that", "testing", "first", "degree", "relatives", "for", "calcium", "levels", "and", "DNA", "sequencing", "may", "have", "a", "role", "in", "the", "assessment", "of", "elderly", "patients", "with", "parathormone-related", "hypercalcemia.", "Introduction", "Familial", "hypocalciuric", "hypercalcemia", "(FHH)", "is", "a", "rare", "autosomal", "dominant", "disease", "that", "runs", "a", "benign", "course.", "Its", "prevalence", "is", "not", "clearly", "established", "[1].", "It", "is", "impor-", "tant", "to", "differentiate", "it", "from", "the", "much", "more", "common", "pri-", "mary", "hyperparathyroidism", "(PHPT)", "to", "avoid", "unnecessary", "and", "potentially", "harmful", "parathyroidectomy", "[2].", "It", "has", "been", "shown", "to", "result", "from", "heterozygous", "inactivating", "mutations", "in", "the", "calcium-sensing", "receptor", "(CaSR)", "gene", "in", "the", "majority", "of", "cases", "[3].", "The", "calcium", "sensing", "receptor", "(CaSR)", "is", "a", "G-protein-coupled", "receptor", "of", "1078", "amino", "acids", "(AAs)", "with", "a", "large", "extracellular", "domain", "and", "the", "characteristic", "seven-transmembrane", "domains", "[4].", "It", "is", "expressed", "in", "the", "parathyroid", "gland,", "kidneys,", "bones,", "and", "other", "tissues", "[5]", "and", "plays", "a", "key", "role", "in", "the", "maintenance", "of", "constant", "levels", "of", "extracellular", "ionized", "calcium.", "It", "modulates", "the", "function", "of", "chief", "cells", "of", "the", "parathyroid", "gland,", "stimulating", "the", "synthesis", "and", "secretion", "of", "PTH", "as", "*", "Correspondence:", "wael@elamin.net", "1Bantry", "General", "Hospital,", "Bantry,", "Co.", "Cork,", "Ireland", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "well", "as", "the", "proliferation", "of", "parathyroid", "cells", "when", "the", "cal-", "cium", "level", "is", "low,", "and", "inhibiting", "these", "functions", "when", "the", "calcium", "level", "is", "high.", "In", "the", "kidneys,", "the", "CaSR", "decreases", "calcium", "reabsorption,", "increases", "calciuresis,", "and", "decreases", "the", "concentrating", "ability", "of", "the", "kidney", "when", "sensing", "hypercalcemia,", "through", "its", "effect", "on", "the", "thick", "ascending", "limb", "of", "the", "loop", "of", "Henle", "and", "on", "the", "medullary", "collecting", "ducts", "[6].", "Two", "hundred", "and", "twenty-three", "mutations", "for", "the", "CaSR", "gene", "are", "listed", "in", "the", "CaSR", "mutation", "database", "[7].", "Of", "these,", "154", "are", "inactivating", "(loss-of-function),", "and", "most", "of", "them", "cause", "FHH", "in", "heterozygous", "and", "neonatal", "severe", "hyperparathyroidism", "(NSHPT)", "in", "homozygous", "patients", "[3].", "Curiously,", "most", "of", "these", "mutations", "are", "con-", "fined", "to", "a", "single", "family,", "with", "only", "a", "few", "having", "been", "described", "in", "more", "than", "one", "family.", "Inactivating", "muta-", "tions", "result", "in", "decreased", "sensing", "of", "calcium", "levels,", "shift-", "ing", "the", "calcium-PTH", "curve", "and", "the", "set-point", "to", "the", "right", "[6].", "Elderly", "patients", "are", "frequently", "affected", "with", "disorders", "of", "calcium", "metabolism", "[8-10].", "Here", "we", "describe", "an", "Irish", "family", "in", "which", "the", "proband", "is", "an", "octogenarian", "with", "hypercalcemia,", "hypocalciuria,", "chronic", "kidney", "disease", "©", "2010", "Elamin", "and", "de", "Buyl;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Kiprono", "et", "al.", "BMC", "Dermatology", "2012,", "12:2", "http://www.biomedcentral.com/1471-5945/12/2", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "Acral", "peeling", "skin", "syndrome", "in", "two", "East-African", "siblings:", "case", "report", "Samson", "K", "Kiprono1*,", "Baraka", "M", "Chaula1†,", "Bernard", "Naafs1,2†", "and", "John", "E", "Masenga1†", "Abstract", "Background:", "Acral", "peeling", "skin", "syndrome", "is", "a", "rare", "autosomal", "recessive", "genodermatosis", "due", "to", "a", "missense", "mutation", "in", "transglutaminase", "5.", "The", "skin", "peeling", "occurs", "at", "the", "separation", "of", "the", "stratum", "corneum", "from", "the", "stratum", "granulosum.", "Case", "presentation:", "We", "present", "a", "case", "of", "two", "siblings", "who", "developed", "continuous", "peeling", "of", "the", "palms", "and", "soles", "from", "the", "first", "year", "of", "life.", "This", "peeling", "was", "more", "severe", "on", "the", "soles", "than", "palms", "and", "on", "younger", "sibling", "than", "elder", "sibling.", "Peeling", "is", "worsened", "by", "occlusion", "and", "sweating.", "Conclusions:", "Sporadic", "cases", "of", "Acral", "Peeling", "Skin", "Syndrome", "occur", "in", "African", "population.", "There", "is", "variability", "in", "time", "of", "presentation", "and", "clinical", "severity", "even", "within", "families.", "Keywords:", "Acral", "peeling", "skin", "syndrome,", "African,", "Siblings", "Background", "Peeling", "Skin", "Syndrome", "is", "a", "rare", "autosomal", "recessive", "skin", "disorder", "characterized", "by", "an", "asymptomatic", "superficial", "exfoliation", "due", "to", "separation", "of", "the", "stratum", "corneum", "[1].", "It", "was", "first", "described", "in", "the", "early", "twentieth", "century", "[2]", "and", "broadly", "classified", "into", "localized", "and", "generalized", "forms.", "The", "generalized", "form", "is", "further", "subdivided", "into", "inflamma-", "tory", "(type", "A)", "and", "non-inflammatory", "(type", "B)", "[3].", "Acral", "Peeling", "Skin", "Syndrome", "(APSS)", "is", "considered", "to", "be", "a", "loca-", "lized", "variant", "[4].", "We", "present", "a", "case", "report", "of", "two", "siblings", "with", "APSS.", "Case", "presentation", "Two", "siblings", "presented", "with", "asymptomatic", "peeling", "of", "the", "hands", "and", "the", "feet.", "The", "elder", "sibling", "was", "a", "13", "year", "old", "boy", "who", "developed", "peeling", "of", "the", "skin", "in", "the", "first", "year", "after", "birth.", "It", "was", "noticed", "that", "the", "peeling", "of", "the", "skin", "left", "a", "soft", "red", "skin,", "which", "progressively", "thickened", "over", "a", "period", "of", "one", "to", "two", "months", "and", "turning", "pale", "before", "peeling", "again", "in", "sheets", "(Figure", "1).", "The", "younger", "sibling", "was", "a", "6", "year", "old", "girl", "who", "had", "peeling", "of", "the", "hands", "and", "feet", "from", "birth.", "The", "problem", "was", "more", "severe", "in", "the", "younger", "sibling", "than", "the", "*", "Correspondence:", "kipsam2@yahoo.com", "†", "Contributed", "equally", "1Department", "of", "Dermatology,", "Regional", "Dermatology", "Training", "Center", "at", "KCMC,", "Box", "8332,", "Moshi,", "Tanzania", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "older", "sibling", "(Figure", "2).", "It", "was", "associated", "with", "hyperhidro-", "sis", "and", "became", "foul", "smelling", "when", "occluded.", "The", "peeling", "of", "the", "skin", "was", "aggravated", "by", "sweating,", "prolonged", "expo-", "sure", "to", "water", "and", "occlusion.", "There", "was", "neither", "associated", "pain", "nor", "pruritus.", "They", "came", "from", "a", "family", "of", "five", "siblings.", "Their", "par-", "ents", "and", "the", "other", "three", "siblings", "did", "not", "have", "a", "similar", "problem.", "It", "was", "a", "consanguineous", "marriage", "of", "first", "cou-", "sins,", "although", "no", "similar", "problem", "among", "their", "family", "members.", "On", "examination,", "the", "siblings", "were", "generally", "in", "good", "health", "with", "normal", "development.", "A", "bilateral", "and", "sym-", "metrical", "peeling", "of", "the", "hands", "and", "the", "feet,", "worse", "on", "the", "palmer", "and", "plantar", "areas", "was", "noted.", "The", "peeling", "extended", "to", "the", "dorsal", "aspects", "of", "both", "the", "hands", "and", "the", "feet.", "The", "pale", "areas", "of", "the", "palms", "could", "be", "peeled", "with", "minimum", "pain", "leaving", "behind", "a", "soft,", "red", "skin.", "The", "peeling", "was", "thicker", "with", "features", "of", "maceration", "in", "the", "younger", "sibling", "(Figure", "3).", "The", "teeth,", "the", "hair", "and", "the", "nails", "were", "normal.", "Skin", "biopsy", "showed", "separation", "of", "stratum", "corneum", "from", "stra-", "tum", "ganulosum", "(Figure", "4).", "Full", "blood", "picture,", "liver", "func-", "tion", "tests", "and", "renal", "function", "tests", "were", "within", "normal", "range.", "A", "diagnosis", "of", "APSS", "was", "made", "and", "both", "siblings", "treated", "with", "topical", "tretinoin", "0.05%", "cream", "for", "four", "months", "without", "any", "improvement.", "©", "2012", "Kiprono", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Available", "online", "http://arthritis-research.com/content/7/5/R1046", "Research", "article", "Vol7No5", "Prevalence", "of", "opioid", "adverse", "events", "in", "chronic", "non-malignant", "pain:", "systematic", "review", "of", "randomised", "trials", "of", "oral", "opioids", "R", "Andrew", "Moore", "and", "Henry", "J", "McQuay", "Open", "Access", "Pain", "Research", "and", "Nuffield", "Department", "of", "Anaesthetics,", "University", "of", "Oxford,", "Oxford", "Radcliffe", "Hospital,", "Oxford,", "UK", "Corresponding", "author:", "R", "Andrew", "Moore,", "andrew.moore@pru.ox.ac.uk", "Received:", "18", "Apr", "2005", "Revisions", "requested:", "18", "May", "2005", "Revisions", "received:", "24", "May", "2005", "Accepted:", "6", "Jun", "2005", "Published:", "28", "Jun", "2005", "Arthritis", "Research", "&", "Therapy", "2005,", "7:R1046-R1051", "(DOI", "10.1186/ar1782)", "This", "article", "is", "online", "at:", "http://arthritis-research.com/content/7/5/R1046", "©", "2005", "Moore", "and", "McQuay;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/", "2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Adverse", "events", "of", "opioids", "may", "restrict", "their", "use", "in", "non-cancer", "pain.", "Analysis", "of", "the", "incidence", "of", "common", "adverse", "events", "in", "trials", "conducted", "in", "non-cancer", "pain", "has", "usually", "been", "limited", "to", "opioids", "used", "to", "treat", "severe", "pain", "according", "to", "the", "WHO", "three-", "step", "ladder.", "To", "examine", "the", "incidence", "of", "common", "adverse", "events", "of", "opioids", "in", "non-cancer", "pain,", "a", "systematic", "review", "and", "meta-analysis", "of", "information", "from", "randomised", "trials", "of", "all", "opioids", "in", "non-cancer", "pain", "was", "undertaken.", "Studies", "used", "were", "published", "randomised", "trials", "of", "oral", "opioid", "in", "non-cancer", "pain,", "with", "placebo", "or", "active", "comparator.", "Thirty-four", "trials", "with", "5,546", "patients", "were", "included", "with", "4,212", "patients", "contributing", "some", "information", "on", "opioid", "adverse", "events.", "Most", "opioids", "used", "(accounting", "for", "90%", "of", "patients)", "were", "for", "treating", "moderate", "Introduction", "Opioids", "are", "advocated", "by", "WHO", "for", "cancer", "pain", "[1],", "but", "their", "role", "in", "chronic", "non-cancer", "pain", "is", "more", "controversial.", "It", "has", "been", "argued", "that", "certain", "types", "of", "chronic", "pain,", "like", "neuro-", "pathic", "pain,", "do", "not", "respond", "to", "opioids", "[2],", "although", "some", "patients", "with", "neuropathic", "pain", "have", "been", "shown", "to", "respond", "well", "to", "opioids,", "as", "do", "patients", "with", "chronic", "nociceptive", "pain", "[3].", "Concerns", "have", "been", "expressed", "about", "the", "safety", "of", "long-", "term", "opioid", "administration", "[4]", "because", "of", "adverse", "effects", "[5],", "development", "of", "tolerance", "to", "the", "analgesic", "effect", "[6],", "addic-", "tion,", "and", "drug", "diversion", "[7].", "Guidelines", "for", "responsible", "use", "of", "opioids", "in", "chronic", "non-cancer", "pain", "[8-10]", "reflect", "concern", "over", "these", "problems.", "At", "least", "one", "recent", "systematic", "review", "has", "investigated", "efficacy", "and", "safety", "of", "oral", "opioids", "in", "placebo-controlled", "randomised", "tri-", "als", "in", "chronic", "non-malignant", "pain", "[11].", "It", "included", "11", "trials", "in", "which", "patients", "received", "different", "oral", "opioids,", "doses,", "and", "dos-", "ing", "regimens,", "over", "varying", "periods", "of", "time,", "and", "in", "patients", "with", "arthritis,", "musculoskeletal", "pain,", "neuropathic", "pain,", "and", "mixed", "rather", "than", "severe", "pain.", "Including", "trials", "without", "a", "placebo", "increased", "the", "amount", "of", "information", "available", "by", "1.4", "times.", "Because", "of", "clinical", "heterogeneity", "in", "condition,", "opioid,", "opioid", "dose,", "duration,", "and", "use", "of", "titration,", "only", "broad", "results", "could", "be", "calculated.", "Use", "of", "any", "oral", "opioid", "produced", "higher", "rates", "of", "adverse", "events", "than", "did", "placebo.", "Dry", "mouth", "(affecting", "25%", "of", "patients),", "nausea", "(21%),", "and", "constipation", "(15%)", "were", "the", "most", "common", "adverse", "events.", "A", "substantial", "proportion", "of", "patients", "on", "opioids", "(22%)", "withdrew", "because", "of", "adverse", "events.", "Because", "most", "trials", "were", "short,", "less", "than", "four", "weeks,", "and", "because", "few", "titrated", "the", "dose,", "these", "results", "have", "limited", "applicability", "to", "longer-term", "use", "of", "opioids", "in", "clinical", "practice.", "Suggestions", "for", "improved", "studies", "are", "made.", "conditions.", "Adverse", "event", "rates", "could", "be", "calculated", "for", "sev-", "eral", "adverse", "events,", "and", "numbers", "needed", "to", "harm", "were", "calcu-", "lated,", "which", "were", "as", "low", "as", "3", "for", "constipation,", "and", "5", "for", "nausea", "and", "somnolence.", "Constipation", "(affecting", "41%),", "nau-", "sea", "(32%)", "and", "somnolence", "(29%)", "were", "the", "most", "common", "adverse", "events.", "The", "fact", "that", "only", "placebo-controlled", "trials", "were", "included", "meant", "that", "any", "trials", "of", "different", "opioids,", "or", "different", "dosing", "regimens,", "or", "different", "formulations", "that", "did", "not", "have", "a", "placebo", "group", "were", "not", "analysed.", "The", "study", "was", "additionally", "limited", "to", "opioids", "(fentanyl,", "hydromorphone,", "methadone,", "morphine,", "oxy-", "codone,", "oxymorphone)", "used", "to", "treat", "severe", "pain", "according", "to", "the", "WHO", "three-step", "ladder,", "and", "did", "not", "include", "other", "opioids,", "like", "codeine,", "dextropoxyphene,", "or", "tramadol,", "often", "used", "to", "treat", "moderate", "pain.", "The", "limited", "number", "of", "trials", "also", "meant", "that", "sensitivity", "analysis", "for", "different", "conditions", "(arthritis,", "muscu-", "loskeletal,", "or", "neuropathic", "pain)", "was", "not", "feasible.", "R1046" ]

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[ "Salgado", "et", "al.", "Retrovirology", "2010,", "7:94", "http://www.retrovirology.com/content/7/1/94", "S", "H", "O", "R", "T", "R", "E", "P", "O", "R", "T", "Open", "Access", "Evolution", "of", "the", "HIV-1", "nef", "gene", "in", "HLA-B*57", "Positive", "Elite", "Suppressors", "Maria", "Salgado1,", "Timothy", "P", "Brennan1,", "Karen", "A", "O’Connell1,", "Justin", "R", "Bailey1,", "Stuart", "C", "Ray1,", "Robert", "F", "Siliciano1,2,", "Joel", "N", "Blankson1*", "Abstract", "Elite", "controllers", "or", "suppressors", "(ES)", "are", "HIV-1", "infected", "patients", "who", "maintain", "viral", "loads", "of", "<", "50", "copies/ml", "without", "antiretroviral", "therapy.", "CD8+", "T", "cells", "are", "thought", "to", "play", "a", "key", "role", "in", "the", "control", "of", "viral", "replication", "and", "exert", "selec-", "tive", "pressure", "on", "gag", "and", "nef", "in", "HLA-B*57", "positive", "ES.", "We", "previously", "showed", "evolution", "in", "the", "gag", "gene", "of", "ES", "which", "surprisingly", "was", "mostly", "due", "to", "synonymous", "mutations", "rather", "than", "non-synonymous", "mutation", "in", "targeted", "CTL", "epitopes.", "This", "finding", "could", "be", "the", "result", "of", "structural", "constraints", "on", "Gag,", "and", "we", "therefore", "examined", "the", "less", "conserved", "nef", "gene.", "We", "found", "slow", "evolution", "of", "nef", "in", "plasma", "virus", "in", "some", "ES.", "This", "evolution", "is", "mostly", "due", "to", "synonymous", "mutations", "and", "occurs", "at", "a", "rate", "similar", "to", "that", "seen", "in", "the", "gag", "gene", "in", "the", "same", "patients.", "The", "results", "provide", "further", "evidence", "of", "ongoing", "viral", "replication", "in", "ES", "and", "suggest", "that", "the", "nef", "and", "gag", "genes", "in", "these", "patients", "respond", "similarly", "to", "selective", "pressure", "from", "the", "host.", "Findings", "The", "mechanisms", "responsible", "for", "the", "control", "of", "the", "HIV-", "1", "replication", "in", "elite", "suppressors", "are", "not", "fully", "under-", "stood", "[1-3].", "Replication", "competent", "virus", "has", "been", "isolated", "from", "some", "ES", "[4-6]", "and", "genotypic", "[4],", "phenoty-", "pic", "[4],", "and", "epidemiologic", "[7]", "analyses", "have", "suggested", "that", "these", "isolates", "are", "generally", "fully", "pathogenic.", "Thus", "it", "appears", "that", "in", "many", "cases,", "host", "factors", "rather", "than", "infection", "with", "defective", "virus", "are", "responsible", "for", "the", "elite", "control", "of", "viral", "replication.", "The", "HLA-B*57", "allele", "is", "overrepresented", "in", "ES", "[8-14]", "which", "suggests", "an", "impor-", "tant", "role", "of", "CD8+", "T", "cells.", "These", "cells", "have", "been", "shown", "to", "exert", "selective", "pressure", "on", "HLA-B*57", "restricted", "epi-", "topes", "in", "ES", "[15-17]", "and", "LTNPs", "[18],", "and", "we", "have", "pre-", "viously", "documented", "evidence", "of", "evolution", "in", "the", "gag", "gene", "in", "plasma", "virus", "of", "HLA-B*57", "positive", "ES", "over", "a", "5", "year", "period", "[19].", "However,", "some", "studies", "have", "sug-", "gested", "that", "Gag", "is", "preferentially", "targeted", "by", "CD8+", "T", "cells", "in", "patients", "who", "control", "viremia", "[12,20]", "and", "it", "is", "therefore", "possible", "that", "viral", "evolution", "in", "ES", "is", "limited", "to", "this", "gene.", "To", "test", "this", "hypothesis,", "we", "analyzed", "proviral", "and", "plasma", "nef", "sequences", "in", "ES", "over", "a", "6", "year", "period", "and", "compared", "the", "rate", "of", "evolution", "in", "these", "two", "*", "Correspondence:", "jblanks@jhmi.edu", "1Department", "of", "Medicine,", "Johns", "Hopkins", "University", "School", "of", "Medicine.", "733", "N.", "Broadway,", "Baltimore", "MD", "21205,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "compartments", "to", "the", "rate", "of", "evolution", "of", "observed", "for", "the", "gag", "gene.", "Four", "previously", "described", "HLA-B*57", "ES", "patients", "were", "studied", "[16,21].", "Viral", "RNA", "was", "isolated", "from", "plasma,", "and", "genomic", "DNA", "was", "purified", "from", "resting", "CD4+", "T", "cells", "as", "described", "previously", "[16].", "To", "limit", "PCR", "resampling,", "nef", "genes", "were", "amplified", "from", "provirus", "in", "genomic", "DNA", "and", "from", "plasma-derived", "RNA", "by", "limiting", "dilution", "“digital”", "nested", "PCR", "using", "previously", "described", "primers", "and", "con-", "ditions", "[21].", "PCR", "products", "were", "directly", "sequenced", "using", "an", "ABI", "PRISM", "3700", "DNA", "analyzer", "(Applied", "Biosystems).", "Chromatograms", "were", "manually", "examined", "for", "the", "pre-", "sence", "of", "double", "peaks", "indicative", "of", "two", "templates", "per", "sequencing", "reaction.", "Such", "sequences", "were", "discarded.", "Sequences", "were", "assembled", "using", "CodonCode", "Aligner,", "version", "1.3.1,", "aligned", "using", "ClustalX,", "and", "the", "alignments", "were", "manually", "adjusted", "in", "Bioedit.", "Sequences", "were", "trans-", "lated", "in", "Bioedit,", "and", "the", "mean", "number", "of", "amino", "acid", "dif-", "ferences", "between", "all", "provirus", "nef", "and", "all", "plasma", "virus", "nef", "sequences", "from", "each", "patient", "was", "calculated.", "Phylogenetic", "analysis", "and", "statistics", "All", "independent", "clonal", "sequences", "obtained", "were", "included", "in", "the", "phylogenetic", "analysis,", "with", "the", "exception", "of", "sequences", "showing", "APOBEC3G/F-mediated", "hyper-", "mutation,", "which", "were", "removed.", "Sequences", "[GenBank:", "FJ430356", "to", "FJ430471", "and", "HQ448774", "to", "HQ448852]", "©", "2010", "Salgado", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Glycobiology", "vol.", "21", "no.", "12", "pp.", "1651–1662,", "2011", "doi:10.1093/glycob/cwr101", "Advance", "Access", "publication", "on", "August", "1,", "2011", "4", "Is", "N-acetyl-D-glucosamine", "a", "rigid", "C1", "chair?", "Benedict", "M", "Sattelle", "and", "Andrew", "Almond1", "Manchester", "Interdisciplinary", "Biocentre,", "131", "Princess", "Street,", "Manchester", "M1", "7DN,", "UK", "Received", "on", "June", "3,", "2011;", "revised", "on", "June", "28,", "2011;", "accepted", "on", "July", "19,", "2011", "Understanding", "microsecond-timescale", "dynamics", "is", "crucial", "to", "establish", "three-dimensional", "(3D)", "structure–activity", "relationships", "in", "sugars", "but", "has", "been", "intractable", "to", "exper-", "iments", "and", "simulations.", "As", "a", "consequence,", "whether", "argu-", "ably", "the", "most", "important", "chemical", "scaffold", "in", "glycobiology,", "N-acetyl-D-glucosamine", "(GlcNAc),", "deviates", "from", "a", "rigid", "4C1", "chair", "is", "unknown.", "Here,", "conformer", "populations", "and", "exchange", "kinetics", "were", "quantified", "from", "the", "longest", "aqueous", "carbohydrate", "simulations", "to", "date", "(0.2", "ms", "total)", "of", "GlcNAc,", "four", "derivatives", "from", "heparan", "sulfate", "and", "their", "methylglycosides.", "Unmodified", "GlcNAc", "took", "3–5", "μs", "to", "reach", "a", "conformational", "equilibrium,", "which", "comprised", "a", "metastable", "4C1", "chair", "that", "underwent", "4C1", "↔", "1C4", "transitions", "at", "a", "predicted", "forward", "rate", "of", "0.8", "μs−1", "with", "an", "average", "1C4-chair", "lifetime", "of", "3", "ns.", "These", "predictions", "agree", "with", "high-resolution", "crystallography", "and", "nuclear", "magnetic", "res-", "onance", "but", "not", "with", "the", "hypothesis", "that", "GlcNAc", "is", "a", "rigid", "4C1", "chair,", "concluded", "from", "previous", "experimental", "analyses", "and", "non-aqueous", "modeling.", "The", "methylglycoside", "was", "cal-", "culated", "to", "have", "a", "slower", "forward", "rate", "(0.3", "μs−1)", "and", "a", "more", "stable", "4C1", "conformer", "(0.2", "kcal", "mol−1),", "suggesting", "that", "pivotal", "3D", "intermediates", "(", "particularly", "2SO,", "1S5", "and", "B2,5)", "increased", "in", "energy,", "and", "water", "was", "implicated", "as", "a", "major", "cause.", "Sulfonation", "(N-,", "3-O", "and", "6-O)", "significantly", "augmented", "this", "effect", "by", "blocking", "pseudorotation,", "but", "did", "not", "alter", "the", "rotational", "preferences", "of", "hydroyxl", "or", "hydro-", "xymethyl", "groups.", "We", "therefore", "propose", "that", "GlcNAc", "undergoes", "puckering", "exchange", "that", "is", "dependent", "on", "polymerization", "and", "sulfo", "substituents.", "Our", "analyses,", "and", "3D", "model", "of", "the", "equilibrium", "GlcNAc", "conformer", "in", "water,", "can", "be", "used", "as", "dictionary", "data", "and", "present", "new", "opportu-", "nities", "to", "rationally", "modify", "puckering", "and", "carbohydrate", "bioactivity,", "with", "diverse", "applications", "from", "improving", "crop", "yields", "to", "disease", "amelioration.", "Keywords:", "glucosamine", "/", "heparan", "sulfate", "/", "kinetics", "/", "pucker", "/", "simulation", "1To", "whom", "correspondence", "should", "be", "addressed:", "Tel:", "+44-161-306-4199;", "Fax:", "+44-161-306-5201;", "e-mail:", "andrew.almond@manchester.ac.uk", "Introduction", "Understanding", "carbohydrate", "three-dimensional", "(3D)", "structure–", "activity", "relationships", "(SARs)", "is", "a", "difficult", "but", "critical", "mile-", "stone", "in", "glycomics.", "Elucidating", "molecular", "details", "of", "glycan", "equilibrium", "3D", "structure,", "presently", "in", "its", "infancy,", "are", "central", "to", "realizing", "accurate", "SARs", "and", "will", "enable", "rational", "exploita-", "tion", "of", "the", "vast", "medicinal", "and", "industrial", "potential", "of", "polysac-", "charides.", "The", "hexosamine", "chemical", "scaffold", "of", "N-acetyl-D-glucosamine", "(GlcNAc)", "is", "ubiquitous", "and", "mediates", "some", "of", "the", "most", "important", "processes", "in", "glycobiology.", "Consequently,", "establishing", "SARs", "in", "GlcNAc", "and", "its", "deriva-", "tives", "will", "engender", "innumerable", "opportunities", "to", "impact", "some", "of", "the", "most", "challenging", "scientific", "problems", "of", "our", "time.", "For", "example,", "as", "well", "as", "being", "a", "versatile", "scaffold", "for", "novel", "drug", "discovery", "(Wang", "et", "al.", "2009),", "chemically", "modified", "GlcNAc", "is", "present", "in", "chitin", "and", "glycosaminoglycans,", "which", "hold", "great", "potential", "as", "novel", "biomaterials", "and", "medicines", "(Gama", "et", "al.", "2006;", "Murrey", "and", "Hsieh-Wilson", "2008;", "Khoushab", "and", "Yamabhai", "2010).", "The", "3D", "structures", "of", "GlcNAc", "polysaccharides", "are", "defined", "by", "two", "dynamic", "conformational", "determinants:", "glycosidic", "linkage", "geometry", "and", "pyranose", "ring", "conformation", "(or", "pucker).", "Nanosecond", "gycosidic-linkage", "dynamics", "are", "better", "understood", "because", "they", "are", "amenable", "to", "study", "by", "both", "nuclear", "magnetic", "resonance", "(NMR)", "spectroscopy", "and", "simulation.", "However,", "while", "puckering", "is", "central", "to", "glycobiology,", "e.g.", "ribose", "differs", "from", "deoxyribose", "by", "having", "different", "equilibrium", "confor-", "mations", "(Rich", "2003),", "whether", "substituents", "affect", "the", "ensemble", "of", "pyranose", "ring", "conformers", "remains", "enigmatic", "because", "exchange", "occurs", "on", "microsecond", "timescales,", "which", "has", "been", "problematic", "for", "NMR", "and", "simulations,", "until", "recently", "(Sattelle", "et", "al.", "2010).", "There", "is", "circumstantial", "experimental", "evidence", "to", "suggest", "that", "pyranoses,", "such", "as", "glucose", "and", "GlcNAc", "(considered", "to", "exist", "as", "exclusively", "stable", "4C1", "chairs),", "are", "not", "as", "stable", "as", "once", "thought.", "For", "example,", "atomic", "force", "microscopy", "has", "inferred", "that", "glucose", "polymers", "contain", "non-4C1", "geometries", "(Marszalek", "et", "al.", "1998;", "Heymann", "and", "Grubmuller", "1999;", "Li", "et", "al.", "1999),", "and", "non-4C1", "GlcNAc", "is", "observed", "in", "high-", "resolution", "crystallographic", "3D", "structures", "of", "diverse", "(non-enzyme)", "protein", "co-complexes", "(Ikemizu", "et", "al.", "1999;", "Chang", "et", "al.", "2003;", "Maveyraud", "et", "al.", "2009;", "Xu", "et", "al.", "2010).", "Furthermore,", "studies", "have", "also", "shown", "that", "appar-", "ently", "stable", "4C1", "chairs", "can", "be", "perturbed", "by", "chemical", "modi-", "fications,", "e.g.", "glucuronic", "acid", "(β-D-GlcA)", "deviates", "from", "a", "4C1", "chair", "in", "fully", "O-sulfonated", "chondroitin", "and", "hyaluronan", "(Wessel", "and", "Bartsch", "1995;", "Maruyama", "et", "al.", "1998;", "Toida", "et", "al.", "1999,", "2000).", "©", "2011", "The", "Author(s).", "Published", "by", "Oxford", "University", "Press.", "All", "rights", "reserved.This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecom-", "mons.org/licenses/by-nc/2.5),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "1651" ]

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[ "RESEARCH", "Waterbor", "ne", "Outbreak", "of", "Norwalk-Like", "Virus", "Gastroenteritis", "at", "a", "Tourist", "Resor", "t,", "Italy", "Delia", "Boccia,*", "Alberto", "Eugenio", "Tozzi,*", "Benvon", "Cotter,*§", "Caterina", "Rizzo,†", "Teresa", "Russo,‡", "Gabriele", "Buttinelli,*", "Alfredo", "Caprioli,*", "Maria", "Luisa", "Marziano,*", "and", "Franco", "Maria", "Ruggeri*", "In", "July", "2000,", "an", "outbreak", "of", "gastroenteritis", "occurred", "at", "a", "tourist", "resort", "in", "the", "Gulf", "of", "Taranto", "in", "southern", "Italy.", "Illness", "in", "344", "people,", "69", "of", "whom", "were", "staff", "members,", "met", "the", "case", "definition.", "Norwalk-like", "virus", "(NLV)", "was", "found", "in", "22", "of", "28", "stool", "specimens", "tested.", "The", "source", "of", "illness", "was", "likely", "contaminated", "drinking", "water,", "as", "environmental", "inspection", "identified", "a", "breakdown", "in", "the", "resort", "water", "system", "and", "tap", "water", "sam-", "ples", "were", "contaminated", "with", "fecal", "bacteria.", "Attack", "rates", "were", "increased", "(51.4%)", "in", "staff", "members", "involved", "in", "water", "sports.", "Relative", "risks", "were", "significant", "only", "for", "exposure", "to", "beach", "showers", "and", "consuming", "drinks", "with", "ice.", "Although", "Italy", "has", "no", "surveillance", "system", "for", "nonbacterial", "gastroenteritis,", "no", "outbreak", "caused", "by", "NLV", "has", "been", "described", "previously", "in", "the", "country.", "N", "virus", "(NLV)", "in", "the", "Caliciviridae", "family,", "which", "includes", "a", "orwalk", "virus", "is", "the", "prototype", "of", "the", "genus", "Norwalk-like", "large", "number", "of", "genetically", "related", "strains", "that", "together", "repre-", "sent", "the", "most", "important", "cause", "of", "gastroenteritis", "outbreaks", "worldwide", "(1–2).", "NLV", "accounts", "for", "up", "to", "96%", "of", "outbreaks", "of", "nonbacterial", "gastroenteritis", "in", "the", "United", "States", "(3)", "and", "has", "been", "implicated", "in", "43%", "of", "all", "foodborne", "outbreaks", "in", "England,", "67%", "in", "Sweden,", "and", "80%", "in", "the", "Netherlands", "(4–6).", "Outbreaks", "of", "NLV", "gastroenteritis", "more", "frequently", "affect", "adults", "and", "children", ">5", "years", "of", "age.", "Because", "of", "the", "low", "infec-", "tious", "dose", "of", "the", "agent", "(10–100", "viral", "particles", "can", "induce", "symptoms),", "outbreaks", "are", "characterized", "by", "a", "high", "secondary", "attack", "rate", "(7).", "In", "most", "documented", "outbreaks,", "the", "incubation", "period", "has", "been", "reported", "as", "24–48", "hours;", "the", "average", "duration", "of", "symptoms", "is", "12–60", "hours.", "During", "an", "outbreak,", ">50%", "of", "infected", "persons", "have", "symptoms", "of", "vomiting,", "most", "often", "in", "combination", "with", "diarrhea", "(8).", "The", "main", "source", "of", "infection", "is", "usually", "contaminated", "food", "or", "water", "(9–13),", "while", "the", "usual", "mode", "of", "transmission", "is", "direct", "person-to-person", "contact", "with", "saliva,", "vomit,", "or", "aerosols.", "Transmission", "may", "also", "occur", "through", "contact", "with", "contaminated", "objects", "and", "surfaces", "such", "as", "showers,", "sinks,", "mats,", "and", "floors", "(3).", "In", "Italy,", "which", "has", "no", "surveillance", "system", "for", "nonbacterial", "gastroenteritis,", "the", "impact", "of", "NLV", "infection", "is", "unknown,", "and", "no", "previous", "outbreaks", "of", "confirmed", "NLV", "infection", "have", "been", "reported.", "We", "describe", "a", "large", "outbreak", "of", "gastroenteritis", "caused", "by", "NLV", "at", "a", "resort", "in", "Italy.", "Methods", "The", "outbreak", "occurred", "at", "a", "tourist", "resort", "in", "the", "Gulf", "of", "Taranto,", "southern", "Italy,", "during", "July", "7–31,", "2000", "(Figure", "1).", "The", "*Istituto", "Superiore", "di", "Sanità,", "Rome,", "Italy;", "†University", "of", "Bari,", "Bari,", "Italy;", "‡Local", "Health", "Unit,", "Montalbano", "Jonico,", "Matera,", "Italy;", "and", "§European", "Programme", "for", "Intervention", "Epidemiology", "Training", "(EPIET),", "Rome,", "Italy", "resort", "has", "an", "area", "of", "122", "hectares", "with", "456", "guest", "rooms", "in", "19", "buildings,", "in", "addition", "to", "staff", "quarters.", "The", "buildings", "are", "situ-", "ated", "around", "a", "central", "area", "where", "a", "restaurant,", "a", "swimming", "pool,", "and", "the", "resort", "management", "office", "are", "located.", "The", "resort", "can", "accommodate", "1,000", "guests,", "who", "usually", "arrive", "on", "a", "Satur-", "day", "and", "depart", "1", "or", "2", "weeks", "later,", "resulting", "in", "approximately", "50%", "turnover", "of", "guests", "each", "weekend.", "The", "resort’s", "water", "tank", "is", "supplied", "via", "a", "1-km", "pipe", "con-", "nected", "to", "the", "main", "public", "water", "supply", "(Figure", "2).", "On", "July", "13,", "a", "break", "in", "this", "water", "pipe", "was", "observed", "(Figure", "2,", "point", "2).", "Inspection", "also", "showed", "a", "bypass", "connecting", "the", "tank", "to", "an", "unused", "irrigation", "system", "(Figure", "2,", "points", "4", "and", "5).", "On", "July", "18,", "2000,", "the", "local", "health", "unit", "and", "the", "Institute", "of", "Hygiene", "of", "the", "Faculty", "of", "Medicine", "in", "Bari", "were", "notified", "about", "an", "outbreak", "of", "gastroenteritis", "at", "the", "resort.", "An", "epidemio-", "logic", "investigation", "was", "initiated", "the", "same", "day", "to", "identify", "the", "agent", "and", "the", "mode", "and", "vehicle", "of", "transmission", "and", "to", "Figure", "1.", "Map", "of", "Italy,", "showing", "location", "of", "tourist", "resort", "on", "Gulf", "of", "Taranto.", "Emerging", "Infectious", "Diseases", "•", "Vol.", "8,", "No.", "6,", "June", "2002", "563" ]

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[ "The", "Fixation", "and", "Saccade", "P3", "Sangita", "Dandekar1*¤,", "Jian", "Ding", "3", ",", "Claudio", "Privitera3,", "Thom", "Carney1,3,", "Stanley", "A.", "Klein1,2,3,4", "1", "Vision", "Science", "Graduate", "Program,", "University", "of", "California,", "Berkeley,", "California,", "United", "States", "of", "America,", "2", "Helen", "Wills", "Neuroscience", "Institute,", "University", "of", "California,", "Berkeley,", "California,", "United", "States", "of", "America,", "3", "School", "of", "Optometry,", "University", "of", "California,", "Berkeley,", "California,", "United", "States", "of", "America,", "4", "Department", "of", "Bioengineering,", "University", "of", "California,", "Berkeley,", "California,", "United", "States", "of", "America", "Abstract", "Although", "most", "instances", "of", "object", "recognition", "during", "natural", "viewing", "occur", "in", "the", "presence", "of", "saccades,", "the", "neural", "correlates", "of", "objection", "recognition", "have", "almost", "exclusively", "been", "examined", "during", "fixation.", "Recent", "studies", "have", "indicated", "that", "there", "are", "post-saccadic", "modulations", "of", "neural", "activity", "immediately", "following", "eye", "movement", "landing;", "however,", "whether", "post-saccadic", "modulations", "affect", "relatively", "late", "occurring", "cognitive", "components", "such", "as", "the", "P3", "has", "not", "been", "explored.", "The", "P3", "as", "conventionally", "measured", "at", "fixation", "is", "commonly", "used", "in", "brain", "computer", "interfaces,", "hence", "characterizing", "the", "post-", "saccadic", "P3", "could", "aid", "in", "the", "development", "of", "improved", "brain", "computer", "interfaces", "that", "allow", "for", "eye", "movements.", "In", "this", "study,", "the", "P3", "observed", "after", "saccadic", "landing", "was", "compared", "to", "the", "P3", "measured", "at", "fixation.", "No", "significant", "differences", "in", "P3", "start", "time,", "temporal", "persistence,", "or", "amplitude", "were", "found", "between", "fixation", "and", "saccade", "trials.", "Importantly,", "sensory", "neural", "responses", "canceled", "in", "the", "target", "minus", "distracter", "comparisons", "used", "to", "identify", "the", "P3.", "Our", "results", "indicate", "that", "relatively", "late", "occurring", "cognitive", "neural", "components", "such", "as", "the", "P3", "are", "likely", "less", "sensitive", "to", "post", "saccadic", "modulations", "than", "sensory", "neural", "components", "and", "other", "neural", "activity", "occurring", "shortly", "after", "eye", "movement", "landing.", "Furthermore,", "due", "to", "the", "similarity", "of", "the", "fixation", "and", "saccade", "P3,", "we", "conclude", "that", "the", "P3", "following", "saccadic", "landing", "could", "possibly", "be", "used", "as", "a", "viable", "signal", "in", "brain", "computer", "interfaces", "allowing", "for", "eye", "movements.", "Citation:", "Dandekar", "S,", "Ding", "J,", "Privitera", "C,", "Carney", "T,", "Klein", "SA", "(2012)", "The", "Fixation", "and", "Saccade", "P3.", "PLoS", "ONE", "7(11):", "e48761.", "doi:10.1371/journal.pone.0048761", "Editor:", "Markus", "Lappe,", "University", "of", "Muenster,", "Germany", "Received", "May", "29,", "2012;", "Accepted", "October", "1,", "2012;", "Published", "November", "7,", "2012", "Copyright:", "2012", "Dandekar", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "Funding", "for", "this", "research", "was", "provided", "by", "DARPA", "grant", "B8U556562", "and", "NIH", "grant", "RO1", "EY04776.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "sd93@nyu.edu", "¤", "Current", "address:", "Department", "of", "Psychology", "and", "Center", "for", "Neural", "Science,", "New", "York", "University,", "New", "York,", "New", "York,", "United", "States", "of", "America", "Introduction", "You", "are", "walking", "down", "the", "street", "when", "you", "notice", "someone", "waving", "at", "you", "in", "your", "peripheral", "vision.", "You", "make", "an", "eye", "movement", "in", "the", "direction", "of", "the", "waving", "and", "recognize", "a", "friend.", "Scenarios", "such", "as", "the", "above,", "wherein", "a", "moment", "of", "visual", "recognition", "is", "preceded", "by", "a", "saccade,", "are", "quite", "commonplace.", "On", "average,", "humans", "make", "2–3", "saccades", "a", "second", "[1,2]", "and", "natural", "vision", "is", "undoubtedly", "a", "dynamic,", "active", "process.", "However,", "most", "studies", "of", "the", "neural", "correlates", "of", "visual", "object", "recognition,", "and,", "more", "specifically", "of", "the", "P3", "EEG", "signal,", "are", "conducted", "in", "situations", "in", "which", "the", "subject", "passively", "fixates", "while", "objects", "are", "presented", "at", "the", "fovea.", "Herein,", "experiments", "are", "presented", "that", "attempt", "to", "equate", "visual", "stimulus", "characteristics", "in", "an", "object", "recognition", "task", "conducted", "at", "fixation", "and", "in", "an", "object", "recognition", "task", "requiring", "a", "saccade.", "It", "was", "hypothesized", "that", "the", "P3", "observed", "after", "a", "saccade", "landing", "would", "differ", "in", "amplitude,", "latency", "and/or", "persistence", "from", "the", "fixation", "P3.", "This", "hypothesis", "was", "based", "on", "a", "variety", "of", "past", "work", "that", "demonstrated", "that", "visual", "processing", "is", "altered", "around", "the", "time", "of", "a", "saccade,", "with", "various", "past", "research", "observing", "modulations", "of", "neural", "responses", "and", "visual", "perception", "occurring", "prior", "to", "a", "saccade", "[3–5]", "and", "post-saccadic", "modulations", "of", "neural", "activity", "occurring", "after", "saccadic", "landing", "[4,6–9].", "Saccade", "related", "modu-", "lations", "in", "neural", "activity", "have", "been", "found", "to", "be", "both", "diverse", "and", "complex.", "For", "example,", "recordings", "in", "macaque", "MSTd", "hint", "at", "a", "complex", "interplay", "between", "modulations", "of", "evoked", "visual", "responses", "and", "modulations", "of", "background", "spontaneous", "firing", "rates", "in", "the", "time", "periods", "immediately", "before", "and", "after", "saccades", "[10].", "Interestingly,", "in", "the", "presence", "of", "saccades,", "depending", "on", "the", "presence", "or", "absence", "of", "visual", "stimulation,", "both", "decreases", "in", "BOLD", "signal", "as", "well", "as", "increases", "in", "BOLD", "signal", "have", "been", "observed", "in", "human", "LGN", "and", "V1", "[11].", "Furthermore,", "various", "groups", "have", "hypothesized", "that", "object", "recognition", "and", "attention", "orienting", "could", "be", "enhanced", "after", "a", "saccade", "due", "to", "the", "known", "coupling", "of", "attention", "and", "saccades", "[12,13].", "Based", "on", "the", "post-saccadic", "modulations", "described", "in", "past", "studies,", "it", "was", "hypothesized", "that", "the", "saccadic", "P3", "could", "be", "enhanced", "in", "amplitude", "and/or", "decreased", "in", "latency", "relative", "to", "the", "fixation", "P3.", "Importantly,", "past", "electrophysiological", "evidence", "for", "post-saccadic", "modulation", "has", "mainly", "been", "quantified", "by", "directly", "comparing", "neural", "activity", "after", "a", "saccade", "to", "a", "baseline", "level", "of", "neural", "activity", "measured", "at", "fixation.", "Given", "that", "there", "are", "a", "multitude", "of", "neural", "processes", "that", "are", "thought", "to", "occur", "after", "a", "saccade", "but", "not", "during", "fixation", "(for", "example,", "the", "updating", "of", "gaze-centered", "coordinate", "systems", "[14]", "and", "the", "occipital", "saccadic", "lambda", "response", "[15,16]),", "the", "functional", "role(s)", "of", "such", "post-saccadic", "modulations", "remain", "unclear.", "In", "contrast,", "herein,", "rather", "than", "comparing", "saccade", "and", "fixation", "neural", "data", "directly,", "we", "instead", "compared", "the", "difference", "of", "the", "target", "and", "distracter", "post-saccadic", "neural", "signals", "(the", "saccade", "P3)", "and", "the", "difference", "of", "the", "target", "and", "distracter", "signals", "measured", "at", "fixation", "(the", "fixation", "P3).", "Any", "general", "changes", "in", "neural", "activity", "due", "to", "the", "occurrence", "of", "a", "saccade", "(as", "well", "as", "the", "EOG", "artifacts", "known", "to", "co-occur", "with", "saccades", "in", "EEG)", "were", "therefore", "expected", "PLOS", "ONE", "|", "www.plosone.org", "1", "November", "2012", "|", "Volume", "7", "|", "Issue", "11", "|", "e48761" ]

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[ "Weng", "et", "al.", "BMC", "Bioinformatics", "2010,", "11:565", "http://www.biomedcentral.com/1471-2105/11/565", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Reanalyze", "unassigned", "reads", "in", "Sanger", "based", "metagenomic", "data", "using", "conserved", "gene", "adjacency", "Francis", "C", "Weng1,", "Chien-Hao", "Su2,3,4,", "Ming-Tsung", "Hsu2,", "Tse-Yi", "Wang2,3,", "Huai-Kuang", "Tsai2,3*,", "Daryi", "Wang1*", "Abstract", "Background:", "Investigation", "of", "metagenomes", "provides", "greater", "insight", "into", "uncultured", "microbial", "communities.", "The", "improvement", "in", "sequencing", "technology,", "which", "yields", "a", "large", "amount", "of", "sequence", "data,", "has", "led", "to", "major", "breakthroughs", "in", "the", "field.", "However,", "at", "present,", "taxonomic", "binning", "tools", "for", "metagenomes", "discard", "30-40%", "of", "Sanger", "sequencing", "data", "due", "to", "the", "stringency", "of", "BLAST", "cut-offs.", "In", "an", "attempt", "to", "provide", "a", "comprehensive", "overview", "of", "metagenomic", "data,", "we", "re-analyzed", "the", "discarded", "metagenomes", "by", "using", "less", "stringent", "cut-offs.", "Additionally,", "we", "introduced", "a", "new", "criterion,", "namely,", "the", "evolutionary", "conservation", "of", "adjacency", "between", "neighboring", "genes.", "To", "evaluate", "the", "feasibility", "of", "our", "approach,", "we", "re-analyzed", "discarded", "contigs", "and", "singletons", "from", "several", "environments", "with", "different", "levels", "of", "complexity.", "We", "also", "compared", "the", "consistency", "between", "our", "taxonomic", "binning", "and", "those", "reported", "in", "the", "original", "studies.", "Results:", "Among", "the", "discarded", "data,", "we", "found", "that", "23.7", "±", "3.9%", "of", "singletons", "and", "14.1", "±", "1.0%", "of", "contigs", "were", "assigned", "to", "taxa.", "The", "recovery", "rates", "for", "singletons", "were", "higher", "than", "those", "for", "contigs.", "The", "Pearson", "correlation", "coefficient", "revealed", "a", "high", "degree", "of", "similarity", "(0.94", "±", "0.03", "at", "the", "phylum", "rank", "and", "0.80", "±", "0.11", "at", "the", "family", "rank)", "between", "the", "proposed", "taxonomic", "binning", "approach", "and", "those", "reported", "in", "original", "studies.", "In", "addition,", "an", "evaluation", "using", "simulated", "data", "demonstrated", "the", "reliability", "of", "the", "proposed", "approach.", "Conclusions:", "Our", "findings", "suggest", "that", "taking", "account", "of", "conserved", "neighboring", "gene", "adjacency", "improves", "taxonomic", "assignment", "when", "analyzing", "metagenomes", "using", "Sanger", "sequencing.", "In", "other", "words,", "utilizing", "the", "conserved", "gene", "order", "as", "a", "criterion", "will", "reduce", "the", "amount", "of", "data", "discarded", "when", "analyzing", "metagenomes.", "Background", "The", "investigation", "of", "metagenomes,", "which", "sequences", "DNA", "from", "mixed", "environmental", "samples", "directly,", "has", "provided", "insights", "into", "microbial", "communities,", "and", "is", "now", "widely", "used", "to", "study", "various", "living", "microorganisms", "as", "a", "system", "[1-4].", "The", "major", "goal", "of", "metagenomic", "stu-", "dies", "is", "to", "determine", "the", "systemic", "properties", "of", "a", "micro-", "bial", "community,", "including", "the", "genetic,", "metabolic,", "ecological,", "physiological", "and", "behavioral", "aspects", "of", "all", "community", "members", "[5-8].", "Some", "high-throughput", "pipe-", "lines", "have", "been", "constructed", "for", "high-performance", "com-", "putational", "analysis", "of", "metagenomic", "data", "[9,10].", "The", "pipelines", "facilitate", "taxonomic", "binning", "of", "huge", "amounts", "*", "Correspondence:", "hktsai@iis.sinica.edu.tw;", "dywang@gate.sinica.edu.tw", "1Biodiversity", "Research", "Center,", "Academia", "Sinica,", "Taipei,", "115,", "Taiwan", "2Institute", "of", "Information", "Science,", "Academia", "Sinica,", "Taipei,", "115,", "Taiwan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "of", "sequencing", "data", "by", "referring", "to", "databases", "of", "known", "microbial", "genomes", "[11-14].", "Based", "on", "the", "above", "approaches,", "recent", "investigations", "have", "revealed", "enor-", "mous", "variations", "among", "the", "microbiomes", "of", "diverse", "environments,", "such", "as", "human", "intestinal", "and", "salivary", "microbiota", "[15-17],", "microbial", "communities", "growing", "on", "sunken", "whale", "skeletons", "[18],", "and", "open", "ocean", "commu-", "nities", "[19,20].", "To", "study", "genetic", "materials", "from", "natural", "environmental", "samples,", "Sanger", "sequencing", "technologies", "have", "been", "used", "for", "generating", "DNA", "sequences", "[15,16,20].", "Yet,", "much", "more", "metagenomic", "datasets", "were", "conducted", "using", "next", "generation", "sequencing", "(NGS)", "technologies", "(e.g.,", "Roche", "GS-FLX,", "Illumina", "1G", "analyzer,", "and", "Applied", "Biosystems", "SOLiD)", "which", "yield", "shorter", "fragments", "ranging", "from", "30", "bp", "to", "350", "bp", "[21].", "As", "huge", "amount", "of", "sequencing", "data", "were", "produced,", "analysis", "tools", "have", "become", "a", "critical", "©", "2010", "Weng", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Jorgensen", "et", "al.", "Malaria", "Journal", "2010,", "9:59", "http://www.malariajournal.com/content/9/1/59", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "High", "heterogeneity", "in", "Plasmodium", "falciparum", "risk", "illustrates", "the", "need", "for", "detailed", "mapping", "to", "guide", "resource", "allocation:", "a", "new", "malaria", "risk", "map", "of", "the", "Lao", "People’s", "Democratic", "Republic", "Pernille", "Jorgensen1*,", "Simone", "Nambanya1,", "Deyer", "Gopinath2,", "Bouasy", "Hongvanthong1,", "Kongxay", "Luangphengsouk1,", "David", "Bell3,", "Samlane", "Phompida1,", "Rattanaxay", "Phetsouvanh4", "Abstract", "Background:", "Accurate", "information", "on", "the", "geographical", "distribution", "of", "malaria", "is", "important", "for", "efficient", "resource", "allocation.", "The", "Lao", "People’s", "Democratic", "Republic", "has", "experienced", "a", "major", "decline", "in", "malaria", "morbidity", "and", "mortality", "in", "the", "past", "decade.", "However,", "efforts", "to", "respond", "effectively", "to", "these", "changes", "have", "been", "impeded", "by", "lack", "of", "detailed", "data", "on", "malaria", "distribution.", "In", "2008,", "a", "countrywide", "survey", "on", "Plasmodium", "falciparum", "diagnosed", "in", "health", "centres", "and", "villages", "was", "initiated", "to", "develop", "a", "detailed", "P.", "falciparum", "risk", "map", "with", "the", "aim", "to", "identify", "priority", "areas", "for", "malaria", "control,", "estimate", "population", "at", "risk,", "and", "guide", "resource", "allocation", "in", "the", "Lao", "People’s", "Democratic", "Republic.", "Methods:", "P.", "falciparum", "incidence", "data", "were", "collected", "from", "point-referenced", "villages", "and", "health", "centres", "for", "the", "period", "2006-2008", "during", "a", "country-wide", "survey", "between", "December", "2008", "and", "January", "2009.", "Using", "the", "highest", "recorded", "annual", "rate,", "continuous", "surfaces", "of", "P.", "falciparum", "incidence", "were", "produced", "by", "the", "inverse", "distance", "weighted", "interpolation", "technique.", "Results:", "Incidence", "rates", "were", "obtained", "from", "3,876", "villages", "and", "685", "health", "centres.", "The", "risk", "map", "shows", "that", "P.", "falciparum", "is", "highly", "heterogeneous", "in", "the", "northern", "and", "central", "regions", "of", "the", "country", "with", "large", "areas", "of", "no", "transmission.", "In", "the", "southern", "part,", "transmission", "is", "pervasive", "and", "the", "risk", "of", "P.", "falciparum", "is", "high.", "It", "was", "estimated", "that", "3.4", "million", "people", "(60%", "of", "the", "population)", "live", "at", "risk", "of", "malaria.", "Conclusions:", "This", "paper", "presents", "the", "first", "comprehensive", "malaria", "risk", "map", "of", "the", "Lao", "People’s", "Democratic", "Republic", "based", "entirely", "on", "empirical", "data.", "The", "estimated", "population", "at", "risk", "is", "substantially", "lower", "than", "previous", "estimates,", "reflecting", "the", "presence", "of", "vast", "areas", "with", "focal", "or", "no", "malaria", "transmission", "as", "identified", "in", "this", "study.", "These", "findings", "provide", "important", "guidance", "for", "malaria", "control", "interventions", "in", "the", "Lao", "People’s", "Democratic", "Republic,", "and", "underline", "the", "need", "for", "detailed", "data", "on", "malaria", "to", "accurately", "predict", "risk", "in", "countries", "with", "heterogeneous", "transmission.", "Background", "Malaria", "risk", "mapping", "is", "increasingly", "being", "utilized", "by", "national", "malaria", "programmes", "as", "a", "tool", "for", "planning", "and", "guiding", "malaria", "control", "strategies", "[1-6].", "Detailed", "knowl-", "edge", "of", "the", "geographical", "extent", "of", "malaria", "and", "intensity", "of", "transmission", "can", "guide", "decisions", "on", "appropriate", "and", "*", "Correspondence:", "pernille.jorgensen@gmail.com", "1Center", "for", "Malariology,", "Parasitology", "and", "Entomology,", "Ministry", "of", "Health,", "Ban", "Chanthabouly,", "Vientiane,", "Lao", "People’s", "Democratic", "Republic", "cost-effective", "control", "strategies,", "allow", "monitoring", "of", "the", "impact", "of", "interventions,", "identify", "areas", "with", "epidemic", "potential,", "and", "provide", "more", "accurate", "estimates", "of", "the", "burden", "of", "disease", "and", "population", "at", "risk.", "In", "the", "Lao", "People’s", "Democratic", "Republic", "(Lao", "PDR),", "malaria", "is", "considered", "endemic", "throughout", "the", "country,", "but", "intensity", "of", "transmission", "is", "known", "to", "vary", "between", "different", "ecological", "zones;", "from", "very", "low", "transmission", "in", "the", "plains", "along", "the", "Mekong", "river", "and", "in", "areas", "of", "high", "©", "2010", "Jorgensen", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Oncology", "Volume", "2009,", "Article", "ID", "981679,", "12", "pages", "doi:10.1155/2009/981679", "Review", "Article", "Understanding", "and", "Targeting", "the", "Eukaryotic", "Translation", "Initiation", "Factor", "eIF4E", "in", "Head", "and", "Neck", "Cancer", "Biljana", "Culjkovic", "and", "Katherine", "L.", "Borden", "Institute", "for", "Research", "in", "Immunology", "and", "Cancer", "and", "Department", "of", "Pathology", "and", "Cell", "Biology,", "Universit´e", "de", "Montr´eal,", "Montreal,", "QC,", "Canada", "H4M", "1J6", "Correspondence", "should", "be", "addressed", "to", "Katherine", "L.", "Borden,", "katherine.borden@umontreal.ca", "Received", "1", "March", "2009;", "Accepted", "30", "September", "2009", "Recommended", "by", "Amanda", "Psyrri", "The", "eukaryotic", "translation", "initiation", "factor", "eIF4E", "is", "elevated", "in", "about", "30%", "of", "human", "malignancies", "including", "HNSCC", "where", "its", "levels", "correlate", "with", "poor", "prognosis.", "Here,", "we", "discuss", "the", "biochemical", "and", "molecular", "underpinnings", "of", "the", "oncogenic", "potential", "of", "eIF4E.", "Studies", "in", "human", "leukemia", "specimens,", "and", "later", "in", "a", "mouse", "model", "of", "prostate", "cancer,", "strongly", "suggest", "that", "cells", "with", "elevated", "eIF4E", "develop", "an", "oncogene", "dependency", "to", "it,", "making", "them", "more", "sensitive", "to", "targeting", "eIF4E", "than", "normal", "cells.", "We", "describe", "several", "strategies", "that", "have", "been", "suggested", "for", "eIF4E", "targeting", "in", "the", "clinic:", "the", "use", "of", "a", "small", "molecule", "antagonist", "of", "eIF4E", "(ribavirin),", "siRNA", "or", "antisense", "oligonucleotide", "strategies,", "suicide", "gene", "therapy,", "and", "the", "use", "of", "a", "tissue-targeting", "4EBP", "fusion", "peptide.", "The", "first", "clinical", "trial", "targeting", "eIF4E", "indicates", "that", "ribavirin", "effectively", "targets", "eIF4E", "in", "poor", "prognosis", "leukemia", "patients", "and", "more", "importantly", "leads", "to", "striking", "clinical", "responses", "including", "complete", "and", "partial", "remissions.", "Finally,", "we", "discuss", "the", "relevance", "of", "these", "findings", "to", "HNSCC.", "Copyright", "©", "2009", "B.", "Culjkovic", "and", "K.", "L.", "Borden.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "1.", "Generalized", "Role", "for", "eIF4E", "in", "Cancer", "The", "eukaryotic", "translation", "initiation", "factor", "4E", "(eIF4E)", "is", "a", "protein", "that", "plays", "a", "central", "role", "in", "the", "regulation", "of", "gene", "expression", "at", "the", "posttranscriptional", "level.", "eIF4E", "binds", "the", "7-", "methyl", "guanosine", "“m7G", "cap”", "structure", "found", "on", "the", "5", "end", "of", "mRNAs.", "In", "the", "cytoplasm,", "eIF4E", "catalyses", "cap-dependent", "protein", "synthesis", "[1,", "2].", "Importantly,", "eIF4E", "effects", "the", "translation", "of", "some", "mRNAs,", "known", "as", "eIF4E", "sensitive,", "more", "than", "other", "transcripts.", "For", "instance,", "elevated", "eIF4E", "levels", "selectively", "increase", "translation", "of", "mRNAs", "coding", "for", "a", "variety", "of", "potent", "growth", "stimulatory", "proteins", "such", "as", "VEGF,", "Pim-1,", "and", "ornithine", "decarboxylase", "(ODC)", "[3–5].", "In", "the", "nucleus,", "eIF4E", "mediates", "in", "the", "export", "of", "another", "subset", "of", "mRNAs", "(such", "as", "cyclin", "D1", "and", "ODC", "mRNAs)", "to", "the", "cytoplasm", "[5–7].", "Thus", "eIF4E", "can", "modulate", "gene", "expression", "at", "two", "levels:", "by", "exporting", "mRNAs", "to", "the", "cytoplasm", "increasing", "their", "concentration", "therein", "and", "by", "enhancing", "the", "translational", "efficiency", "of", "transcripts", "that", "are", "already", "in", "the", "cytoplasm.", "Not", "all", "transcripts", "are", "affected", "at", "both", "levels.", "Importantly,", "eIF4E", "requires", "its", "m7G", "cap", "binding", "function", "in", "order", "to", "act", "in", "either", "of", "these", "functions.", "Clearly,", "dysregulation", "of", "eIF4E", "will", "profoundly", "affect", "the", "cellular", "proteome.", "The", "process", "of", "malignant", "transformation", "requires", "multi-", "ple", "molecular", "events", "involving", "activation", "of", "proto-oncogene", "products", "that", "stimulate", "growth", "and", "inactivation", "of", "suppres-", "sor", "genes", "that", "inhibit", "cellular", "proliferation.", "Together,", "these", "events", "result", "in", "selective", "dysregulation", "of", 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[ "Acta", "Myologica", "•", "2012;", "XXXI:", "p.", "156-160", "MeMorIes", "by", "a", "MyologIst", "Introducing", "corticosteroids", "therapy", "from", "1969", "to", "1990", "at", "the", "Centre/Institute", "for", "Neuromuscular", "Diseases,", "KbC", "rebro,", "Zagreb,", "Croatia", "Anica", "Jušić", "Retired", "Professor", "of", "Neurology", "The", "author", "presents", "the", "chronological", "development", "of", "therapy", "by", "corticosteroids", "in", "myasthenia", "gravis", "(MG),", "as", "well", "as", "dilem-", "mas", "connected", "to", "this", "kind", "of", "treatment", "at", "the", "Centre/Insti-", "tute", "Zagreb,", "she", "founded.", "The", "improvement", "of", "postoperative", "prognosis", "of", "thymectomy", "with", "corticosteroids", "is", "described", "and", "transfer", "of", "positive", "experiences", "to", "other", "neurological", "diseases.", "The", "side", "effects", "can", "be", "reduced", "significantly", "by", "respecting", "the", "basic", "rules:", "the", "choice", "of", "corticosteroids", "(fluocortolone,", "meth-", "yprednisolone,", "no", "dexamethasone),", "single", "dose", "administered", "in", "the", "morning,", "not", "later", "than", "8", "a.m.", "(respecting", "the", "circadian", "rhythm", "of", "concentration", "of", "cortisol", "in", "blood).", "Initially,", "the", "high", "dose", "is", "administered", "daily,", "until", "the", "stabilisation", "of", "signs", "and", "symptoms", "improvement.", "Then,", "in", "my", "early", "modification,", "the", "initial", "dose,", "administered", "every", "other", "day,", "becames", "gradually", "lowered.", "The", "diet", "is", "similar", "to", "diabetic,", "with", "the", "potassium", "add-", "ed.", "In", "the", "period", "from", "1973", "to", "1990,", "212", "myasthenia", "gravis", "and", "37", "polymyositis", "patients", "were", "treated", "that", "way.", "We", "recommend", "to", "continue", "endocrinological", "research,", "on", "which", "we", "already", "reported,", "now", "with", "contemporary", "methods.", "The", "value", "of", "the", "“pulse", "therapy”", "should", "be", "analysed", "in", "more", "details,", "with", "peroral", "corticosteroids", "added", "afterwards.", "Key", "words:", "Myasthenia", "gravis,", "corticosteroids", "Introduction", "In", "the", "60’s", "of", "the", "last", "century,", "myasthenia", "indeed", "was", "a", "“gravis”", "disease.", "It", "used", "to", "be", "treated", "with", "a-n", "ticholinesterase", "drugs", "and", "thymectomy,", "the", "kinds", "of", "therapy,", "that", "used", "to", "raise", "numerous", "controversies.", "Thymectomy", "was", "at", "that", "time", "an", "operation", "with", "a", "high", "degree", "of", "probability", "for", "a", "postoperative", "deterioration.", "Myasthenic", "crises", "were", "very", "frequent", "and", "tracheotomies", "repeatedly", "indicated.", "ACTH", "therapy", "Thanks", "to", "Professor", "Albrecht", "Struppler,", "my", "teacher", "of", "electromyography", "from", "Münich,", "I", "met", "K.", "Osserman,", "during", "the", "World", "Congress", "of", "Neurology,", "New", "York,", "1969.", "At", "that", "time", "he", "was", "regarded", "as", "top", "MG", "expert,", "ac-", "tive", "at", "the", "Mount", "Sinai", "Hospital,", "New", "York.", "He", "was", "the", "first", "to", "start", "treating", "MG", "with", "a", "series", "of", "ACTH", "injections.", "At", "first,", "the", "course", "would", "cause", "dete-", "rioration,", "followed", "by", "a", "significant", "and", "long-lasting", "im-", "provement.", "Upon", "my", "return", "to", "Zagreb,", "I", "tried", "to", "intro-", "duce", "that", "kind", "of", "therapy", "at", "my", "unit.", "The", "deterioration", "would", "sometimes", "reach", "to", "the", "respiratory", "crisis,", "so", "there", "was", "no", "way", "of", "treatment", "on", "a", "“regular”", "neurological", "de-", "partment.", "I", "started", "to", "alocate", "the", "patients", "on", "the", "Intensive", "Care", "of", "the", "Department", "for", "Infectious", "Diseases", "chaired", "by", "J.", "Rulnjević,", "where", "we", "usually", "sent", "the", "patients", "during", "myasthenic", "crises.", "Upon", "the", "constitution", "of", "the", "Thoracic", "Surgery", ",", "Jordanovac,", "Zagreb,", "with", "LJ.", "Topalović,", "the", "head,", "I", "would", "transfer", "them", "there.", "Our", "ACTH", "course", "was", "followed", "by", "azathioprin", "(Im-u", "ran),", "introduced", "into", "therapy", "of", "myasthenia", "gravis", "in", "1969", "at", "the", "Neurological", "Department,", "Hamburg,", "Germany.", "A-p", "plied", "as", "first", "and", "only", "therapy", "no", "convincing", "positive-", "ef", "fects", "were", "found.", "However,", "after", "ACTH", "series,", "it", "prolonged", "the", "remission.", "The", "ACTH", "therapy", "was", "a", "complicated", "one,", "risky,", "and", "in", "the", "end,", "the", "results", "were", "not", "as", "desired.", "HSDAD", "therapy", "In", "1973", "I", "visited", "the", "Bethesda", "hospital,", "where", "I", "met", "W.", "King", "Engel.", "He", "gave", "me", "a", "very", "useful", "information", "about", "HSDAD", "(High", "Single", "Dose", "Alternate", "Day)", "predni-", "Address", "for", "correspondence:", "Anica", "Jušić,", "MD,", "Gundulićeva", "ul.", "49,", "10000", "Zagreb,", "Croatia.", "E-mail:", "anica.jusic@gmail.com.hr", "156" ]

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[ "BMC", "Medical", "Research", "Methodology", "Research", "article", "Statistical", "methods", "to", "correct", "for", "verification", "bias", "in", "diagnostic", "studies", "are", "inadequate", "when", "there", "are", "few", "false", "negatives:", "a", "simulation", "study", "Angel", "M", "Cronin*", "and", "Andrew", "J", "Vickers", "BioMed", "Central", "Open", "Access", "Address:", "Department", "of", "Epidemiology", "and", "Biostatistics", "and", "Department", "of", "Surgery,", "Memorial", "Sloan-Kettering", "Cancer", "Center,", "1275", "York", "Avenue,", "NY,", "NY", "10021,", "USA", "Email:", "Angel", "M", "Cronin*", "-", "serioa@mskcc.org;", "Andrew", "J", "Vickers", "-", "vickersa@mskcc.org", "*", "Corresponding", "author", "Published:", "11", "November", "2008", "BMC", "Medical", "Research", "Methodology", "2008,", "8:75", "doi:10.1186/1471-2288-8-75", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2288/8/75", "Received:", "26", "June", "2008", "Accepted:", "11", "November", "2008", "©", "2008", "Cronin", "and", "Vickers;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "A", "common", "feature", "of", "diagnostic", "research", "is", "that", "results", "for", "a", "diagnostic", "gold", "standard", "are", "available", "primarily", "for", "patients", "who", "are", "positive", "for", "the", "test", "under", "investigation.", "Data", "from", "such", "studies", "are", "subject", "to", "what", "has", "been", "termed", "\"verification", "bias\".", "We", "evaluated", "statistical", "methods", "for", "verification", "bias", "correction", "when", "there", "are", "few", "false", "negatives.", "Methods:", "A", "simulation", "study", "was", "conducted", "of", "a", "screening", "study", "subject", "to", "verification", "bias.", "We", "compared", "estimates", "of", "the", "area-under-the-curve", "(AUC)", "corrected", "for", "verification", "bias", "varying", "both", "the", "rate", "and", "mechanism", "of", "verification.", "Results:", "In", "a", "single", "simulated", "data", "set,", "varying", "false", "negatives", "from", "0", "to", "4", "led", "to", "verification", "bias", "corrected", "AUCs", "ranging", "from", "0.550", "to", "0.852.", "Excess", "variation", "associated", "with", "low", "numbers", "of", "false", "negatives", "was", "confirmed", "in", "simulation", "studies", "and", "by", "analyses", "of", "published", "studies", "that", "incorporated", "verification", "bias", "correction.", "The", "2.5th", "–", "97.5th", "centile", "range", "constituted", "as", "much", "as", "60%", "of", "the", "possible", "range", "of", "AUCs", "for", "some", "simulations.", "Conclusion:", "Screening", "programs", "are", "designed", "such", "that", "there", "are", "few", "false", "negatives.", "Standard", "statistical", "methods", "for", "verification", "bias", "correction", "are", "inadequate", "in", "this", "circumstance.", "Background", "A", "common", "feature", "of", "diagnostic", "research", "is", "that", "results", "for", "a", "diagnostic", "gold", "standard", "are", "available", "only", "for", "patients", "who", "are", "positive", "for", "the", "test", "under", "investigation.", "Prostate-", "specific", "antigen", "(PSA)", "testing", "is", "a", "typical", "example:", "we", "want", "to", "know", "the", "operating", "characteristics", "of", "the", "PSA", "test,", "but", "men", "are", "only", "recommended", "for", "biopsy", "(the", "gold", "standard", "assessment", "of", "prostate", "cancer)", "if", "their", "PSA", "is", "above", "a", "specified", "threshold,", "such", "as", "4", "ng/ml.", "Accordingly", "we", "have", "little", "information", "on", "whether", "men", "with", "PSA", "less", "than", "4", "mg/ml", "do", "or", "do", "not", "have", "prostate", "cancer.", "True", "dis-", "ease", "state", "is", "therefore", "known", "for", "only", "a", "subset", "of", "partici-", "pants,", "and", "because", "that", "subset", "is", "determined", "by", "the", "diagnostic", "test", "result,", "data", "are", "subject", "to", "what", "has", "been", "termed", "\"verification", "bias\"[1].", "Verification", "bias", "is", "associ-", "ated", "particularly", "with", "screening", "tests:", "screening", "a", "healthy", "population", "for", "a", "symptomless", "disease", "will,", "by", "definition,", "result", "in", "further", "diagnostic", "work", "up", "only", "for", "those", "with", "a", "positive", "screening", "test.", "Begg", "and", "Greenes", "have", "proposed", "straightforward", "Baye-", "sian", "methods", "to", "correct", "for", "verification", "bias", "[1,2].", "Their", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "BMC", "Geriatrics", "Research", "article", "Subcutaneous", "dextrose", "for", "rehydration", "of", "elderly", "patients", "–", "an", "evidence-based", "review", "Tari", "Turner*1", "and", "Anne-Marie", "Cassano2", "Address:", "1Centre", "for", "Clinical", "Effectiveness,", "Monash", "Institute", "of", "Health", "Services", "Research,", "Monash", "Medical", "Centre,", "Clayton,", "Victoria,", "Australia", "and", "2Rehabilitation", "and", "Aged", "Care", "Services,", "Kingston", "Centre,", "Cheltenham,", "Victoria,", "Australia", "Email:", "Tari", "Turner*", "-", "tari.turner@med.monash.edu.au;", "Anne-Marie", "Cassano", "-", "Annemarie.cassano@southernhealth.org.au", "*", "Corresponding", "author", "BioMed", "Central", "Open", "Access", "Published:", "15", "April", "2004", "BMC", "Geriatrics", "2004,", "4:2", "Received:", "02", "December", "2003", "Accepted:", "15", "April", "2004", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2318/4/2", "©", "2004", "Turner", "and", "Cassano;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "all", "media", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Abstract", "Background:", "In", "the", "Rehabilitation", "and", "Aged", "Care", "Services", "Program", "at", "Southern", "Health", "in", "Victoria,", "saline", "hypodermoclysis", "is", "a", "relatively", "common", "method", "of", "rehydration.", "However,", "there", "were", "questions", "about", "the", "safety", "and", "effectiveness", "of", "subcutaneous", "infusion", "of", "other", "fluids", "and,", "in", "particular,", "dextrose", "solutions.", "This", "review", "aimed", "to", "assess", "the", "safety", "and", "effectiveness", "of", "rehydration", "of", "elderly", "patients", "with", "subcutaneous", "5%", "dextrose", "solutions", "compared", "with", "intravenous", "5%", "dextrose", "solutions.", "Methods:", "We", "searched", "the", "Cochrane", "Library,", "Medline,", "IDIS,", "CINAHL,", "Current", "Contents,", "Premedline,", "Australasian", "Medical", "Index,", "the", "Joanna", "Briggs", "Institute,", "the", "US", "National", "Guideline", "Clearinghouse", "and", "bibliographies", "of", "retrieved", "articles.", "Searching", "was", "undertaken", "in", "July", "2003.", "Studies", "selected", "were", "primary", "studies", "(or", "systematic", "reviews", "of", "primary", "studies)", "providing", "evidence", "as", "to", "the", "effectiveness", "and", "safety", "of", "subcutaneous", "infusion", "of", "dextrose", "solutions", "for", "rehydration", "of", "elderly", "patients.", "We", "included", "articles", "published", "in", "English", "in", "the", "last", "10", "years.", "Data", "were", "extracted", "by", "a", "single", "researcher.", "Results:", "From", "our", "search", "we", "identified", "15", "potentially", "relevant", "articles.", "We", "obtained", "the", "full", "text", "of", "these", "articles", "to", "determine", "their", "relevance.", "After", "application", "of", "the", "inclusion", "criteria,", "four", "articles", "remained", "for", "appraisal", "including", "one", "systematic", "review,", "two", "randomised", "controlled", "trials", "and", "one", "cohort", "study.", "Conclusion:", "The", "four", "studies", "appraised", "all", "provide", "evidence", "that", "appropriate", "volumes", "of", "subcutaneous", "dextrose", "infusions", "(in", "the", "form", "of", "half-normal", "saline-glucose", "5%,", "40", "g/L", "dextrose", "and", "30", "mmol/L", "NaCl,", "or", "5%", "dextrose", "solution", "and", "4", "g/L", "NaCl,", "or", "two-thirds", "5%", "glucose", "and", "one-third", "normal", "saline)", "can", "be", "used", "effectively", "for", "the", "treatment", "of", "dehydration,", "with", "similar", "rates", "of", "adverse", "effects", "to", "intravenous", "infusion.", "The", "evidence", "in", "this", "area", "is", "limited,", "and", "larger", "randomised", "controlled", "trials", "using", "validated", "outcome", "measures", "would", "be", "useful", "to", "confirm", "these", "results.", "Background", "Hypodermoclysis,", "or", "subcutaneous", "fluid", "infusion,", "was", "widely", "used", "to", "treat", "dehydration", "in", "the", "first", "half", "of", "last", "century.", "However", "after", "reports", "of", "severe", "adverse", "reactions", "in", "the", "1950s", "[1],", "predominantly", "resulting", "from", "infusion", "of", "hypertonic", "solutions,", "hypodermoclysis", "fell", "into", "disre-", "pute", "and", "then", "almost", "entirely", "out", "of", "use.", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Aygören-Pürsün", "et", "al.", "Allergy,", "Asthma", "&", "Clinical", "Immunology", "2010,", "6:21", "http://www.aacijournal.com/content/6/1/21", "R", "E", "S", "E", "A", "R", "C", "H", "ALLERGY,", "ASTHMA", "&", "CLINICAL", "IMMUNOLOGY", "Open", "Access", "On", "demand", "treatment", "and", "home", "therapy", "of", "hereditary", "angioedema", "in", "Germany", "-", "the", "Frankfurt", "experience", "Emel", "Aygören-Pürsün*,", "Inmaculada", "Martinez-Saguer,", "Eva", "Rusicke,", "Thomas", "Klingebiel,", "Wolfhart", "Kreuz", "Abstract", "Background:", "Manifestation", "of", "acute", "edema", "in", "hereditary", "angioedema", "(HAE)", "is", "characterized", "by", "interindividual", "and", "intraindividual", "variability", "in", "symptom", "expression", "over", "time.", "Flexible", "therapy", "options", "are", "needed.", "Methods:", "We", "describe", "and", "report", "on", "the", "outcomes", "of", "the", "highly", "individualized", "approach", "to", "HAE", "therapy", "practiced", "at", "our", "HAE", "center", "in", "Frankfurt", "(Germany).", "Results:", "The", "HAE", "center", "at", "the", "Frankfurt", "University", "Hospital", "currently", "treats", "450", "adults", "with", "HAE", "or", "AAE", "and", "107", "pediatric", "HAE", "patients", "with", "highly", "individualized", "therapeutic", "approaches.", "73.9%", "of", "the", "adult", "patients", "treat", "HAE", "attacks", "by", "on-demand", "therapy", "with", "pasteurized", "pd", "C1-INH", "concentrate,", "9.8%", "use", "additional", "prophylaxis", "with", "attenuated", "androgens,", "1%", "of", "the", "total", "patient", "population", "in", "Frankfurt", "has", "been", "treated", "with", "Icatibant", "up", "to", "now.", "In", "addition", "adult", "and", "selected", "pediatric", "patients", "with", "a", "high", "frequency", "of", "severe", "attacks", "are", "instructed", "to", "apply", "individual", "replacement", "therapy", "(IRT)", "with", "pasteurized", "pd", "C1-INH", "concentrate.", "Improvement", "on", "Quality", "of", "Life", "items", "was", "shown", "for", "these", "patients", "compared", "to", "previous", "long-term", "danazol", "prophylaxis.", "Home", "treatment", "of", "HAE", "patients", "was", "developed", "in", "the", "Frankfurt", "HAE", "center", "in", "line", "with", "experiences", "in", "hemophilia", "therapy", "and", "has", "so", "far", "been", "implemented", "over", "a", "period", "of", "28", "years.", "At", "present", "248", "(55%)", "of", "the", "adult", "patients", "and", "26", "(24%)", "of", "the", "pediatric", "patients", "are", "practicing", "home", "treatment", "either", "as", "on", "demand", "or", "IRT", "treatment.", "Conclusions:", "In", "conclusion,", "the", "individualized", "home", "therapies", "provided", "by", "our", "HAE", "center,", "aim", "to", "limit", "the", "disruption", "to", "normal", "daily", "activities", "that", "occurs", "for", "many", "HAE", "patients.", "Furthermore,", "we", "seek", "to", "optimize", "the", "economic", "burden", "of", "the", "disease", "while", "offering", "a", "maximum", "quality", "of", "life", "to", "our", "patients.", "Introduction", "On", "demand", "treatment", "of", "acute", "angioedema", "in", "HAE", "type", "I", "and", "II", "Hereditary", "angioedema", "(HAE)", "is", "based", "on", "a", "hereditary,", "life-long", "deficiency", "of", "C1-esterase-inhibitor", "(C1-INH).", "Patients", "with", "HAE", "suffer", "from", "recurrent,", "localized,", "acute", "edema", "attacks", "that", "can", "affect", "any", "body", "location.", "Mainly", "affected", "are", "subcutaneous", "tissues", "or", "mucous", "membranes,", "the", "gastrointestinal", "tract,", "and", "the", "throat,", "the", "latter", "leading", "to", "potentially", "life-threatening", "laryngeal", "edema.", "Manifestation", "of", "acute", "edema", "in", "hereditary", "angioedema", "is", "characterized", "by", "interindividual", "and", "intraindividual", "variability", "in", "symptom", "expression", "over", "*", "Correspondence:", "eap@em.uni-frankfurt.de", "Centre", "of", "Pediatrics", "III,", "Department", "of", "Hematology,", "Oncology", "and", "Hemostasis,", "Comprehensive", "Care", "Centre", "for", "Thrombosis", "and", "Hemostasis,", "Johann", "Wolfgang", "Goethe", "University", "Hospital,", "Frankfurt", "am", "Main,", "Germany", "time.", "The", "onset", "of", "the", "next", "attack,", "its", "location", "and", "its", "severity", "are", "unpredictable.", "Treatment", "options", "adapted", "on", "the", "specific", "needs", "of", "the", "individual", "patient", "need", "to", "be", "implemented", "based", "on", "the", "type", "and", "frequency", "of", "HAE", "attacks", "and", "should", "be", "re-evaluated", "from", "time", "to", "time", "[1,2].", "Worldwide,", "five", "different", "therapy", "options", "for", "on", "demand", "therapy", "of", "acute", "attacks", "based", "on", "three", "distinct", "pathophysiological", "approaches", "are", "currently", "under", "clini-", "cal", "investigation", "or", "already", "approved", "in", "different", "coun-", "tries.", "For", "replacement", "of", "lacking", "or", "dysfunctional", "C1-INH,", "three", "different", "C1-INH", "concentrates", "-", "two", "plasma-derived", "(pd)", "and", "one", "expressed", "in", "transgenic", "rabbits", "-", "are", "available", "or", "under", "investigation.", "Antagon-", "ism", "of", "the", "bradykinin", "B2-receptor,", "which", "is", "supposed", "to", "largely", "convey", "the", "increase", "in", "vascular", "permeability", "lead-", "ing", "to", "acute", "angioedema", "in", "HAE,", "via", "the", "B2-receptor", "©", "2010", "Aygören-Pürsün", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Goodacre", "et", "al.", "Health", "and", "Quality", "of", "Life", "Outcomes", "2012,", "10:20", "http://www.hqlo.com/content/10/1/20", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Health", "utility", "after", "emergency", "medical", "admission:", "a", "cross-sectional", "survey", "Steve", "W", "Goodacre*,", "Richard", "W", "Wilson,", "Mike", "Bradburn,", "Martina", "Santarelli", "and", "Jon", "P", "Nicholl", "Abstract", "Objectives:", "Health", "utility", "combines", "health", "related", "quality", "of", "life", "and", "mortality", "to", "produce", "a", "generic", "outcome", "measure", "reflecting", "both", "morbidity", "and", "mortality.", "It", "has", "not", "been", "widely", "used", "as", "an", "outcome", "measure", "in", "evaluations", "of", "emergency", "care", "and", "little", "is", "known", "about", "the", "feasibility", "of", "measurement,", "typical", "values", "obtained", "or", "baseline", "factors", "that", "predict", "health", "utility.", "We", "aimed", "to", "measure", "health", "utility", "after", "emergency", "medical", "admission,", "to", "compare", "health", "utility", "to", "age,", "gender", "and", "regional", "population", "norms,", "and", "identify", "independent", "predictors", "of", "health", "utility.", "Methods:", "We", "selected", "5760", "patients", "across", "three", "hospitals", "who", "were", "admitted", "to", "hospital", "by", "ambulance", "as", "a", "medical", "emergency.", "The", "EQ-5D", "questionnaire", "was", "mailed", "to", "all", "who", "were", "still", "alive", "30", "days", "after", "admission.", "Health", "utility", "was", "estimated", "by", "applying", "tariff", "values", "to", "the", "EQ-5D", "responses", "or", "imputing", "a", "value", "of", "zero", "for", "those", "who", "had", "died.", "Multivariable", "analysis", "was", "used", "to", "identify", "independent", "predictors", "of", "health", "utility", "at", "30", "days.", "Results:", "Responses", "were", "received", "from", "2488", "(47.7%)", "patients,", "while", "541", "(9.4%)", "had", "died.", "Most", "respondents", "reported", "some", "or", "severe", "problems", "with", "each", "aspect", "of", "health.", "Mean", "health", "utility", "was", "0.49", "(standard", "deviation", "0.35)", "in", "survivors", "and", "0.45", "(0.36)", "including", "non-survivors.", "Some", "75%", "had", "health", "utility", "below", "their", "expected", "value", "(mean", "loss", "0.32,", "95%", "confidence", "interval", "0.31", "to", "0.33)", "and", "11%", "had", "health", "utility", "below", "zero", "(worse", "than", "death).", "On", "multivariable", "modelling,", "reduced", "health", "utility", "was", "associated", "with", "increased", "age", "and", "lower", "GCS,", "varied", "according", "to", "ICD10", "code", "and", "was", "lower", "among", "females,", "patients", "with", "recent", "hospital", "admission,", "steroid", "therapy,", "or", "history", "of", "chronic", "respiratory", "disease,", "malignancy,", "diabetes", "or", "epilepsy.", "Conclusions:", "Health", "utility", "can", "be", "measured", "after", "emergency", "medical", "admission,", "although", "responder", "bias", "may", "be", "significant.", "Health", "utility", "after", "emergency", "medical", "admission", "is", "poor", "compared", "to", "population", "norms.", "We", "have", "identified", "independent", "predictors", "or", "health", "utility", "that", "need", "to", "be", "measured", "and", "taken", "into", "account", "in", "non-", "randomized", "evaluations", "of", "emergency", "care.", "Keywords:", "health", "utility,", "emergency", "medicine,", "hospital", "admission", "Background", "Patient", "outcomes", "need", "to", "be", "measured", "after", "emergency", "medical", "care", "for", "research,", "quality", "improvement", "and", "benchmarking", "of", "performance", "[1].", "Mortality", "is", "widely", "used", "as", "an", "outcome", "measure", "in", "research,", "and", "risk-adjusted", "mortality", "can", "be", "used", "to", "compare", "systems", "of", "emergency", "care", "and", "drive", "quality", "improvement", "[2,3].", "Health", "related", "quality", "of", "life,", "by", "contrast,", "is", "less", "commonly", "used", "as", "an", "outcome", "measure", "in", "emergency", "medicine", "research", "and", "has", "rarely", "been", "used", "in", "quality", "improvement", "[4-7].", "*", "Correspondence:", "s.goodacre@sheffield.ac.uk", "School", "of", "Health", "and", "Related", "Research", "(ScHARR),", "University", "of", "Sheffield,", "Sheffield,", "UK", "However,", "some", "important", "emergency", "interventions,", "such", "as", "thrombolysis", "for", "stroke", "[8],", "affect", "health", "related", "quality", "of", "life", "rather", "than", "mortality.", "The", "impact", "of", "these", "interven-", "tions", "will", "only", "be", "identified", "if", "we", "measure", "health", "related", "quality", "of", "life.", "Health", "related", "quality", "of", "life", "has", "been", "measured", "after", "hospital", "admission", "for", "major", "trauma", "[9-11]", "and", "specific", "ill-", "nesses,", "such", "as", "myocardial", "infarction", "[12]", "and", "stroke", "[13].", "Major", "trauma", "is", "only", "responsible", "for", "a", "small", "proportion", "of", "emergency", "hospital", "admissions.", "Most", "admissions", "are", "for", "medical", "conditions,", "with", "patients", "increasingly", "presenting", "with", "mixed", "pathologies", "and", "multiple", "co-morbidities.", "We", "need", "to", "measure", "health", "related", "quality", "of", "life", "in", "the", "general", "©", "2012", "Goodacre", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "International", "Journal", "of", "Hepatology", "Volume", "2011,", "Article", "ID", "154541,", "11", "pages", "doi:10.4061/2011/154541", "Review", "Article", "Treatment", "of", "Liver", "Metastases", "in", "Patients", "with", "Neuroendocrine", "Tumors:", "A", "Comprehensive", "Review", "Theresa", "R.", "Harring,1", "N.", "Thao", "N.", "Nguyen,1", "John", "A.", "Goss,1,", "2", "and", "Christine", "A.", "O’Mahony1,", "2", "1", "Michael", "E.", "DeBakey", "Department", "of", "Surgery,", "Baylor", "College", "of", "Medicine,", "One", "Baylor", "Plaza,", "Suite", "No.", "404D,", "Houston,", "TX", "77030,", "USA", "2", "Division", "of", "Abdominal", "Transplantation,", "The", "Liver", "Center,", "Michael", "E.", "DeBakey", "Department", "of", "Surgery,", "Baylor", "College", "of", "Medicine,", "1709", "Dryden", "Street,", "Suite", "No.", "1500,", "Houston,", "TX", "77030,", "USA", "Correspondence", "should", "be", "addressed", "to", "Christine", "A.", "O’Mahony,", "comahony@bcm.edu", "Received", "15", "July", "2011;", "Accepted", "10", "August", "2011", "Academic", "Editor:", "Dan", "Granberg", "Copyright", "©", "2011", "Theresa", "R.", "Harring", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Patients", "diagnosed", "with", "Neuroendocrine", "Tumors", "(NET)", "often", "are", "also", "diagnosed", "with", "Neuroendocrine", "Liver", "Metastases", "(NLM)", "during", "the", "course", "of", "their", "disease.", "NLM", "can", "cause", "significant", "morbidity", "and", "mortality,", "oftentimes", "much", "more", "than", "compared", "to", "patients", "with", "NET.", "Treatment", "options", "have", "been", "limited", "in", "the", "past,", "focusing", "on", "surgical", "resections,", "for", "which", "only", "a", "minority", "of", "patients", "are", "candidates.", "However,", "developments", "of", "new", "treatment", "modalities", "have", "progressed", "rapidly", "and", "patients", "with", "NLM", "now", "have", "significantly", "more", "options,", "including", "surgical-directed", "therapies;", "liver-directed", "therapies;", "and", "nonsurgical,", "non-liver-", "directed", "therapies.", "This", "review", "provides", "information", "about", "the", "roles", "of", "hepatic", "resection,", "orthotopic", "liver", "resection,", "radiofrequency", "ablation,", "hepatic", "artery", "embolization", "and", "hepatic", "artery", "chemoembolization,", "hepatic", "artery", "radioembolization", "and", "selective", "internal", "radiation", "therapy,", "peptide", "receptor", "radionuclide", "therapy,", "systemic", "chemotherapy,", "biotherapies", "including", "somatostatin", "analogs", "and", "interferon-α,", "vascular", "endothelial", "growth", "factor", "and", "mTOR", "targets,", "and", "microRNA-regulated", "pathways.", "Given", "these", "new", "options,", "the", "clinician", "can", "tailor", "therapy", "specific", "to", "the", "patient", "diagnosed", "with", "NLM,", "thereby", "giving", "the", "patient", "the", "best", "possible", "chance", "of", "prolonged", "survival.", "1.", "Introduction", "Patients", "with", "Neuroendocrine", "Tumors", "(NETs)", "often", "suffer", "from", "Neuroendocrine", "Liver", "Metastases", "(NLMs)", "causing", "significant", "morbidity", "and", "mortality.", "The", "excess", "hormone", "production,", "the", "multitude", "of", "hepatic", "lesions,", "and", "ultimate", "liver", "disease", "lend", "to", "the", "poorer", "prognosis.", "In", "fact,", "46%–93%", "of", "patients", "with", "NETs", "will", "find", "NLMs", "involved", "at", "the", "time", "of", "diagnosis", "[1].", "Patients", "with", "liver", "metastases", "have", "a", "signifi-", "cantly", "worse", "prognosis", "than", "those", "without", "liver", "involvement.", "The", "5-year", "survival", "of", "patients", "with", "NLMs", "on", "supportive", "care", "is", "0%–20%", "[1–3].", "This", "dismal", "prognosis", "paints", "a", "much", "more", "stark", "reality", "for", "a", "pathological", "process", "often", "described", "as", "“indolent”.", "Surgical", "interventions", "for", "NLMs", "have", "consistently", "been", "shown", "to", "have", "superior", "outcomes", "to", "nonoperative", "therapies.", "Resection", "alone", "is", "supported", "by", "favorable", "long-", "term", "outcomes", "in", "large", "retrospective", "trials", "[2];", "however,", "complete", "surgical", "extirpation", "is", "an", "option", "for", "a", "very", "small", "percentage", "of", "the", "neuroendocrine", "cancer", "patient", "population", "[1].", "Due", "to", "excessive", "metastatic", "tumor", "burden", "in", "difficult", "locations,", "surgical", "resections", "are", "limited", "to", "only", "10%", "of", "these", "patients", "[2].", "Treatment", "options", "for", "patients", "that", "are", "not", "surgical", "candidates", "have", "evolved", "over", "the", "last", "several", "years.", "Use", "of", "ablative", "techniques,", "as", "well", "as", "development", "of", "new", "medical", "therapies,", "has", "expanded", "the", "treatment", "options", "for", "the", "majority", "of", "patients", "with", "NLMs.", "2.", "Surgical-Directed", "Therapies", "Surgery", "remains", "the", "only", "potential", "for", "cure", "in", "patients", "with", "NLMs.", "Even", "in", "the", "setting", "of", "incurable", "disease,", "surgery", "offers", "the", "best", "chance", "for", "prolonged", "survival.", "In", "patients", "treated", "with", "resection,", "the", "five-year", "survival", "has", "been", "shown", "to", "be", "greater", "than", "60%", "[4,", "5]", "and", "even", "approaches", "80%", "in", "some", "studies,", "with", "minimal", "mortality", "(<5%)", "and", "morbidity", "(<30%)", "[6].", "A", "precise", "review", "of", "the", "literature", "available", "on", "patients", "who", "undergo", "liver", "resection", "for", "neuroendocrine" ]

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[ "Diabetology", "&", "Metabolic", "Syndrome", "BioMed", "Central", "Commentary", "Revisiting", "clinical", "trials", "on", "glycemic", "control", "and", "cardiovascular", "risk", "Sandra", "Roberta", "Gouvea", "Ferreira", "Open", "Access", "Address:", "Nutrition", "Department,", "School", "of", "Public", "Health,", "University", "of", "São", "Paulo,", "Brazil", "Email:", "Sandra", "Roberta", "Gouvea", "Ferreira", "-", "sandrafv@usp.br", "Published:", "28", "September", "2009", "Diabetology", "&", "Metabolic", "Syndrome", "2009,", "1:12", "doi:10.1186/1758-5996-1-12", "This", "article", "is", "available", "from:", "http://www.dmsjournal.com/content/1/1/12", "Received:", "26", "April", "2009", "Accepted:", "28", "September", "2009", "©", "2009", "Ferreira;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "The", "most", "relevant", "clinical", "trials,", "assessing", "the", "role", "of", "glycemic", "control", "in", "reducing", "cardiovascular", "risk,", "are", "examined.", "The", "UKPDS", "was", "the", "first", "to", "address", "this", "issue.", "More", "recent", "trials", "(ACCORD,", "ADVANCE", "and", "VADT)", "are", "controversial", "and", "evidences", "did", "not", "support", "that", "strict", "glycemic", "control", "(reflected", "by", "normal", "glycated", "hemoglobin)", "exclusively", "is", "sufficient", "to", "reduce", "cardiovascular", "risk", "in", "complicated", "individuals", "with", "long-term", "type", "2", "diabetes", "mellitus.", "Some", "possible", "reasons", "for", "controversies", "are", "included.", "Commentary", "In", "the", "last", "years,", "an", "increase", "in", "the", "cardiovascular", "mortal-", "ity", "of", "diabetic", "individuals", "has", "been", "observed,", "being", "more", "significant", "among", "diabetic", "women", "[1].", "The", "presence", "of", "diabetes", "mellitus", "has", "a", "deleterious", "effect", "on", "mortality", "independently", "of", "other", "risk", "factors,", "resulting", "in", "a", "two-fold", "increase", "in", "the", "mortality", "rate", "[2].", "Recently,", "Haffner", "et", "al", "[3]", "observed", "that", "diabetes", "is", "considered", "an", "equivalent", "of", "high", "cardiovascular", "risk,", "as", "diabetic", "individuals,", "even", "without", "a", "previous", "cardiovascular", "event,", "present", "an", "inci-", "dence", "of", "myocardial", "infarction", "in", "a", "period", "of", "seven", "years", "similar", "to", "non-diabetic", "individuals", "who", "have", "already", "pre-", "sented", "cardiovascular", "events.", "Since", "the", "1960s,", "several", "clinical", "trials", "evaluated", "the", "role", "of", "glycemic", "control", "in", "decreasing", "cardiovascular", "risk.", "How-", "ever,", "by", "the", "end", "of", "the", "1990s", "and", "especially", "in", "the", "begin-", "ning", "of", "this", "century,", "the", "main", "clinical", "studies", "focusing", "on", "the", "role", "of", "the", "glycemic", "control", "for", "the", "decrease", "of", "cardio-", "vascular", "risk", "were", "conducted,", "such", "as", "the", "UKPDS", "-", "United", "Kingdom", "Prospective", "Diabetes", "Study", "[4]", "and", "Steno-2", "[5].", "In", "this", "review,", "we", "will", "emphasize", "mainly", "the", "three", "latest", "studies:", "the", "ACCORD", "-", "Action", "to", "Control", "Cardiovascular", "Risk", "in", "Diabetes", "[6],", "ADVANCE", "-", "Action", "in", "Diabetes", "and", "Vascular", "Disease", "-", "Preterax", "and", "Diamicron", "Modified", "Release", "Controlled", "Evaluation", "[7]", "and", "VADT", "-", "Veterans", "Affair", "Diabetes", "Trial", "[8].", "The", "UKPDS", "[4]", "was", "the", "first", "of", "these", "studies", "and", "it", "was", "a", "milestone", "in", "diabetology.", "The", "investigators", "observed", "that", "individuals", "submitted", "to", "intensive", "glycemic", "control", "had", "a", "risk", "reduction", "of", "16%,", "which", "was", "not", "significant", "with", "regards", "to", "macrovascular", "events,", "especially", "acute", "myocar-", "dial", "infarction", "and", "sudden", "death.", "UKPDS", "also", "found", "that", "a", "1%", "decrease", "in", "glycated", "hemoglobin", "reduced", "21%", "of", "the", "risk", "of", "any", "diabetes-related", "outcome,", "14%", "the", "risk", "of", "myo-", "cardial", "infarction", "and", "37%", "the", "risk", "of", "microangiopathy", "[9].", "Steno-2", "[5]", "which", "was", "a", "study", "of", "intensive", "interven-", "tion", "in", "multiple", "cardiovascular", "risk", "factors", "in", "type", "2", "dia-", "betic", "individuals", "with", "microalbuminuria,", "showed", "that", "in", "addition", "to", "the", "intensive", "glycemic", "control,", "the", "control", "of", "other", "risk", "factors", "frequently", "observed", "in", "these", "individuals", "such", "as", "hypertension,", "dyslipidemia", "and", "microalbuminu-", "ria,", "significantly", "decreased", "the", "risk", "of", "cardiovascular", "events", "and", "microangiopathy.", "The", "major", "conclusion", "of", "Steno-2", "was", "that", "the", "exclusive", "control", "of", "glycemia", "is", "not", "effective", "for", "the", "cardiovascular", "protection", "in", "type", "2", "diabe-", "tes,", "since", "a", "number", "of", "other", "risk", "factors", "-", "which", "constitute", "the", "metabolic", "syndrome", "-", "must", "be", "also", "intensively", "treated.", "Steno-2", "has", "recently", "reported", "the", "results", "of", "the", "further", "5-", "Page", "1", "of", "4", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Effects", "of", "Current", "Provisional", "Restoration", "Materials", "on", "the", "Viability", "of", "Fibroblasts", "Mustafa", "Ulkera", "H.", "Esra", "Ulkerb", "Mustafa", "Zortukc", "Mehmet", "Bulbuld", "Ali", "Riza", "Tuncdemire", "M.", "Selim", "Bilgine", "AbStRACt", "Objectives:", "The", "aim", "of", "the", "present", "study", "was", "to", "evaluate", "the", "cytotoxic", "effects", "of", "three", "different", "provisional", "restoration", "materials", "on", "fibroblasts.", "Two", "bis-acrylic", "based", "[Tempofit", "Duomix", "(Detax),", "Protemp", "3", "Garant", "(3M", "ESPE)]", "and", "one", "urethan", "dimethacrylate", "[Revotek", "LC", "(GC", "Corporation)]", "based", "provisional", "restoration", "materials", "used.", "Methods:", "Materials", "were", "prepared", "according", "to", "the", "manufacturers’", "instructions", "in", "standard", "teflon", "disks", "(2x5", "mm)", "and", "four", "samples", "were", "extracted", "in", "7", "ml", "of", "Basal", "Medium", "Eagle", "with", "10%", "new", "born", "calf", "serum", "and", "100", "mg/ml", "penicillin/streptomycin", "for", "24", "hours.", "The", "L929", "fibroblast", "cells", "were", "plated", "(25.000", "cells/ml)", "in", "well", "plates,", "and", "maintained", "in", "a", "CO2", "incubator", "at", "37°C", "for", "24h.", "After", "24", "hours,", "the", "incubation", "medium", "was", "replaced", "by", "the", "immersed", "medium", "in", "which", "the", "samples", "were", "stored", "and", "the", "L929", "fibroblasts", "were", "incubated", "in", "contact", "with", "eluates", "for", "24", "hours", "at", "37°C", "for", "24h.", "The", "fibroblast", "cell", "viability", "was", "analyzed", "by", "measuring", "the", "mitochondrial", "activity", "with", "the", "methyltetrazolium", "test", "(MTT).", "Twelve", "well", "used", "for", "each", "specimen", "and", "experiment", "repeated", "for", "two", "times.", "The", "data", "was", "statistically", "analyzed", "by", "Mann-Whitney", "U", "tests.", "Results:", "The", "results", "showed", "that,", "Revotek", "LC", "and", "Protemp", "3", "Garant", "were", "not", "cytotoxic", "for", "fibroblast", "cells", "when", "compared", "to", "control", "group", "(P>.05).", "However,", "Tempofit", "duomix", "was", "cytotoxic", "for", "L929", "fibroblasts", "when", "compared", "to", "control", "group", "and", "other", "tested", "materials", "(P<.05).", "Conclusions:", "Taking", "into", "consideration", "the", "limitations", "of", "an", "in", "vitro", "study,", "our", "study", "indicate", "that", "provisional", "restoration", "materials", "might", "have", "cytotoxic", "effects", "on", "fibroblasts", "and", "should", "be", "selected", "carefully", "for", "clinical", "applications.", "(Eur", "J", "Dent", "2009;3:114-119)", "Key", "words:", "Provisional", "restoration", "materials;", "Cytotoxicity;", "Fibroblast;", "MTT.", "a", "DDS,", "PhD,", "Assistant", "Professor,", "Erciyes", "University,", "Faculty", "of", "Dentistry,", "Department", "of", "Conservative", "Dentistry,", "Kayseri,", "Turkey.", "b", "DDS,", "PhD,", "Research", "Assistant,", "Selcuk", "University,", "Faculty", "of", "Dentistry,", "Department", "of", "Conservative", "Dentistry,", "Konya,", "Turkey.", "c", "DDS,", "PhD,", "Assistant", "Professor,", "Erciyes", "University,", "Faculty", "of", "Dentistry,", "Department", "of", "Prosthetic", "Dentistry,", "Kayseri,", "Turkey.", "d", "DDS,", "PhD,", "Specialist", "in", "Oral", "Health", "Hospital,", "Selcuklu,", "Konya,", "Turkey.", "114", "European", "Journal", "of", "Dentistry", "e", "DDS,", "PhD,", "Selcuk", "University", "Faculty", "of", "Dentistry,", "Department", "of", "Prosthetic", "Dentistry,", "Konya,", "Turkey.", "Corresponding", "author:", "Dr.", "Mustafa", "Ulker", "Erciyes", "University,", "Faculty", "of", "Dentistry,", "Department", "of", "Conservative", "Dentistry,", "38039,", "Campus,", "Kayseri,", "Turkey.", "Phone:", "+", "90", "352", "4374937-29129", "Fax", ":", "+", "90", "352", "4380657", "E-mail:", "muulker@hotmail.com", "or", "mulker@selcuk.edu.tr" ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "5,6,7,8-Tetrahydroquinolin-8-one", "Teodozja", "M.", "Lipin´", "ska,a", "Zbigniew", "Karczmarzyk,a*", "Waldemar", "Wysocki,a", "Ewa", "Grubaa", "and", "Andrzej", "Fruzin´", "skib", "aDepartment", "of", "Chemistry,", "University", "of", "Podlasie,", "ul.", "3", "Maja", "54,", "08-110", "Siedlce,", "Poland,", "and", "bDepartment", "of", "General", "and", "Ecological", "Chemistry,", "Technical", ".", "University,", "ul.", "Zeromskiego", "115,", "90-924", "Ło´", "dz´,", "Poland", "Correspondence", "e-mail:", "kar@uph.edu.pl", "Received", "20", "April", "2011;", "accepted", "28", "April", "2011", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "293", "K;", "mean", "(C–C)", "=", "0.004", "A˚;", "R", "factor", "=", "0.050;", "wR", "factor", "=", "0.153;", "data-to-parameter", "ratio", "=", "7.6.", "In", "the", "quinoline", "fused-ring", "system", "of", "the", "title", "compound,", "C9H9NO,", "the", "pyridine", "ring", "is", "planar", "to", "within", "0.011", "(3)", "A˚", ",", "while", "the", "partially", "saturated", "cyclohexene", "ring", "adopts", "a", "sofa", "conformation", "with", "an", "asymmetry", "parameter", "Cs(C6)", "=", "1.5", "(4)", ".", "There", "are", "no", "classical", "hydrogen", "bonds", "in", "the", "crystal", "structure.", "Molecules", "form", "molecular", "layers", "parallel", "to", "(100)", "with", "a", "distance", "between", "the", "layers", "of", "a/2", "=", "3.468", "A˚", ".", "Related", "literature", "The", "title", "compound", "is", "an", "intermediate", "for", "the", "synthesis", "of", "polyheterocycles", "giving", "photoluminescence", "(Kelly", "&", "Lebedev,", "2002)", "and", "a", "key", "substrate", "to", "synthesis", "of", "its", "8-amino", "substi-", "tuted", "derivatives", "with", "pharmacological", "activity", "(e.g.", "Gudmundsson", "et", "al.,", "2009).", "For", "our", "ongoing", "study", "on", "the", "synthesis", "and", "structure", "of", "condensed", "pyridine", "and", "quinoline", "derivatives,", "see:", "Lipin´", "ska", "(2005);", "Karczmarzyk", "et", "al.", "(2010).", "For", "the", "synthesis,", "see:", "Kelly", "&", "Lebedev", "(2002).", "For", "a", "related", "structure,", "see:", "OXHYQU", "(Cygler", "et", "al.,", "1981).", "For", "structure", "interpretation", "tools,", "see:", "Bruno", "et", "al.", "(2002);", "Spek", "(2009).", "For", "a", "description", "of", "the", "Cambridge", "Structural", "Database,", "see:", "Allen", "(2002).", "For", "bond-length", "data,", "see:", "Allen", "et", "al.", "(1987).", "For", "asymmetry", "parameters,", "see:", "Duax", "&", "Norton", "(1975).", "Experimental", "Crystal", "data", "C9H9NO", "Mr", "=", "147.17", "Orthorhombic,", "P212121", "a", "=", "6.9393", "(2)", "A˚", "b", "=", "8.0885", "(3)", "A˚", "c", "=", "13.4710", "(4)", "A˚", "Data", "collection", "Bruker", "SMART", "APEXII", "CCD", "diffractometer", "Absorption", "correction:", "multi-scan", "(SADABS;", "Bruker,", "2005)", "Tmin", "=", "0.878,", "Tmax", "=", "1.000", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.050", "wR(F", "2)", "=", "0.153", "S", "=", "1.14", "761", "reflections", "organic", "compounds", "V", "=", "756.11", "(4)", "A˚", "3", "Z", "=", "4", "Cu", "K", "radiation", "=", "0.68", "mm", "1", "T", "=", "293", "K", "0.60", "0.16", "0.15", "mm", "5358", "measured", "reflections", "761", "independent", "reflections", "734", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.022", "100", "parameters", "H-atom", "parameters", "constrained", "max", "=", "0.28", "e", "A˚", "3", "min", "=", "0.18", "e", "A˚", "3", "Data", "collection:", "APEX2", "(Bruker,", "2005);", "cell", "refinement:", "SAINT", "(Bruker,", "2005);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEP-3", "for", "Windows", "(Farrugia,", "1997);", "software", "used", "to", "prepare", "material", "for", "publication:", "SHELXL97", "and", "WinGX", "(Farrugia,", "1999).", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "JH2281).", "References", "Allen,", "F.", "H.", "(2002).", "Acta", "Cryst.", "B58,", "380–388.", "Allen,", "F.", "H.,", "Kennard,", "O.,", "Watson,", "D.", "G.,", "Brammer,", "L.,", "Orpen,", "A.", "G.", "&", "Taylor,", "R.", "(1987).", "J.", "Chem.", "Soc.", "Perkin", "Trans.", "2,", "pp.", "S1–19.", "Bruker", "(2005).", "APEX2,", "SAINT", "and", "SADABS.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Bruno,", "I.", "J.,", "Cole,", "J.", "C.,", "Edgington,", "P.", "R.,", "Kessler,", "M.,", "Macrae,", "C.", "F.,", "McCabe,", "P.,", "Pearson,", "J.", "&", "Taylor,", "R.", "(2002).", "Acta", "Cryst.", "B58,", "389–397.", "Cygler,", "M.,", "Dobrynin,", "K.", "&", "Stepien,", "A.", "(1981).", "Cryst.", "Struct.", "Commun.", "10,", "395–398.", "Duax,", "W.", "L.", "&", "Norton,", "D.", "A.", "(1975).", "Atlas", "of", "Steroid", "Structures,", "Vol.", "1,", "pp.", "16–", "19.", "New", "York:", "Plenum", "Press.", "Farrugia,", "L.", "J.", "(1997).", "J.", "Appl.", "Cryst.", "30,", "565.", "Farrugia,", "L.", "J.", "(1999).", "J.", "Appl.", "Cryst.", "32,", "837–838.", "Gudmundsson,", "K.", "S.,", "Sebahar,", "P.", "R.,", "D’Aurora", "Richardson,", "L.,", "Miller,", "J.", "F.,", "Turner,", "E.", "M.,", "Catalono,", "J.", "G.,", "Spaltenstein,", "A.,", "Lawrence,", "W.,", "Thomson,", "M.", "&", "Jenkinson,", "S.", "(2009).", "Bioorg.", "Med.", "Chem.", "Lett.", "19,", "5048–5052.", "Karczmarzyk,", "Z.,", "Lipin´", "ska,", "T.", "M.,", "Wysocki,", "W.,", "Urban´", "czyk-Lipkowska,", "Z.", "&", "Kalicki,", "P.", "(2010).", "Acta", "Cryst.", "E66,", "o806–o807.", "Kelly,", "T.", "R.", "&", "Lebedev,", "R.", "L.", "(2002).", "J.", "Org.", "Chem.", "67,", "2197–2205.", "Lipin´", "ska,", "T.", "M.", "(2005).", "Tetrahedron", "61,", "8148–8158.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Spek,", "A.", "L.", "(2009).", "Acta", "Cryst.", "D65,", "148–155.", "Acta", "Cryst.", "(2011).", "E67,", "o1365", "doi:10.1107/S1600536811016175", "Lipi", "n´ska", "et", "al.", "o1365" ]

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[ "Crea", "et", "al.", "Molecular", "Cancer", "2012,", "11:52", "http://www.molecular-cancer.com/content/11/1/52", "R", "E", "V", "I", "E", "W", "The", "emerging", "role", "of", "histone", "lysine", "demethylases", "in", "prostate", "cancer", "Francesco", "Crea1*,", "Lei", "Sun3,", "Antonello", "Mai4,", "Yan", "Ting", "Chiang1,", "William", "L", "Farrar3,", "Romano", "Danesi2", "and", "Cheryl", "D", "Helgason1,5*", "Open", "Access", "Abstract", "Early", "prostate", "cancer", "(PCa)", "is", "generally", "treatable", "and", "associated", "with", "good", "prognosis.", "After", "a", "variable", "time,", "PCa", "evolves", "into", "a", "highly", "metastatic", "and", "treatment-refractory", "disease:", "castration-resistant", "PCa", "(CRPC).", "Currently,", "few", "prognostic", "factors", "are", "available", "to", "predict", "the", "emergence", "of", "CRPC,", "and", "no", "curative", "option", "is", "available.", "Epigenetic", "gene", "regulation", "has", "been", "shown", "to", "trigger", "PCa", "metastasis", "and", "androgen-independence.", "Most", "epigenetic", "studies", "have", "focused", "on", "DNA", "and", "histone", "methyltransferases.", "While", "DNA", "methylation", "leads", "to", "gene", "silencing,", "histone", "methylation", "can", "trigger", "gene", "activation", "or", "inactivation,", "depending", "on", "the", "target", "amino", "acid", "residues", "and", "the", "extent", "of", "methylation", "(me1,", "me2,", "or", "me3).", "Interestingly,", "some", "histone", "modifiers", "are", "essential", "for", "PCa", "tumor-", "initiating", "cell", "(TIC)", "self-renewal.", "TICs", "are", "considered", "the", "seeds", "responsible", "for", "metastatic", "spreading", "and", "androgen-", "independence.", "Histone", "Lysine", "Demethylases", "(KDMs)", "are", "a", "novel", "class", "of", "epigenetic", "enzymes", "which", "can", "remove", "both", "repressive", "and", "activating", "histone", "marks.", "KDMs", "are", "currently", "grouped", "into", "7", "major", "classes,", "each", "one", "targeting", "a", "specific", "methylation", "site.", "Since", "their", "discovery,", "KDM", "expression", "has", "been", "found", "to", "be", "deregulated", "in", "several", "neoplasms.", "In", "PCa,", "KDMs", "may", "act", "as", "either", "tumor", "suppressors", "or", "oncogenes,", "depending", "on", "their", "gene", "regulatory", "function.", "For", "example,", "KDM1A", "and", "KDM4C", "are", "essential", "for", "PCa", "androgen-dependent", "proliferation,", "while", "PHF8", "is", "involved", "in", "PCa", "migration", "and", "invasion.", "Interestingly,", "the", "possibility", "of", "pharmacologically", "targeting", "KDMs", "has", "been", "demonstrated.", "In", "the", "present", "paper,", "we", "summarize", "the", "emerging", "role", "of", "KDMs", "in", "regulating", "the", "metastatic", "potential", "and", "androgen-dependence", "of", "PCa.", "In", "addition,", "we", "speculate", "on", "the", "possible", "interaction", "between", "KDMs", "and", "other", "epigenetic", "effectors", "relevant", "for", "PCa", "TICs.", "Finally,", "we", "explore", "the", "role", "of", "KDMs", "as", "novel", "prognostic", "factors", "and", "therapeutic", "targets.", "We", "believe", "that", "studies", "on", "histone", "demethylation", "may", "add", "a", "novel", "perspective", "in", "our", "efforts", "to", "prevent", "and", "cure", "advanced", "PCa.", "Keywords:", "Prostate", "cancer,", "Epigenetics,", "Tumor-initiating", "cells,", "Histone", "demethylase,", "Androgen", "receptor", "Introduction:", "prostate", "cancer", "epigenetics", "It", "has", "been", "estimated", "that", "240,890", "men", "in", "the", "US", "devel-", "oped", "prostate", "cancer", "(PCa)", "during", "2011", "[1].", "In", "western", "countries,", "PCa", "is", "the", "most", "common", "male", "neoplasm,", "and", "the", "second", "leading", "cause", "of", "male", "cancer-related", "deaths.", "Unlike", "other", "common", "neoplasms", "(lung", "and", "colon", "can-", "cer),", "PCa", "incidence", "has", "increased", "in", "the", "past", "few", "years.", "PCa", "is", "a", "double-stage", "disease,", "which", "usually", "starts", "as", "a", "treatable", "and", "poorly", "aggressive", "neoplasm.", "Early", "PCa", "can", "be", "treated", "by", "a", "combination", "of", "surgery,", "radiation", "and", "*", "Correspondence:", "fcrea@bccrc.ca;", "chelgaso@bccrc.ca", "1Experimental", "Therapeutics,", "British", "Columbia", "Cancer", "Research", "Centre,", "675", "West", "10th", "Avenue,", "Vancouver,", "BC,", "Canada", "V5Z", "1L3", "5Department", "of", "Surgery,", "Faculty", "of", "Medicine,", "University", "of", "British", "Columbia,", "910", "West", "10th", "Avenue,", "Vancouver,", "BC,", "Canada", "V5Z", "4E3", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "hormonal", "therapy", "[2].", "The", "last", "option", "includes", "castra-", "tion", "and", "pharmacological", "disruption", "of", "androgen-", "receptor", "(AR)", "signalling,", "which", "is", "a", "major", "proliferation", "stimulus", "for", "prostate", "cells.", "After", "a", "variable", "time,", "PCa", "may", "evolve", "into", "an", "aggressive", "neoplasm,", "usually", "referred", "to", "as", "castration-resistant", "PCa", "(CRPC)", "[3].", "CRPC", "is", "asso-", "ciated", "with", "metastasis", "to", "lung,", "brain,", "liver", "and", "bones", "in", "90%", "of", "the", "cases,", "and", "displays", "an", "18-month", "median", "sur-", "vival", "[4].", "CRPC", "is", "resistant", "to", "conventional", "treatments,", "and", "chemotherapy", "itself", "can", "only", "delay", "its", "progression.", "Currently,", "few", "molecular", "targets", "are", "available", "to", "treat", "CRPC", "[3],", "and", "few", "prognostic", "factors", "are", "associated", "with", "PCa", "recurrence", "and", "progression", "[5].", "Thus,", "the", "identifica-", "tion", "of", "novel", "prognostic", "factors", "and", "therapeutic", "targets", "is", "highly", "needed", "in", "this", "field.", "©", "2012", "Crea", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "BMC", "Cancer", "Research", "article", "Suppression", "subtractive", "hybridization", "profiles", "of", "radial", "growth", "phase", "and", "metastatic", "melanoma", "cell", "lines", "reveal", "novel", "potential", "targets", "Josane", "F", "Sousa", "and", "Enilza", "M", "Espreafico*", "BioMed", "Central", "Open", "Access", "Address:", "Department", "of", "Cellular", "and", "Molecular", "Biology", "and", "Pathogenic", "Bioagents", "of", "the", "Faculty", "of", "Medicine", "of", "Ribeirão", "Preto", "–", "University", "of", "São", "Paulo,", "Ribeirão", "Preto,", "SP,", "Brazil", "Email:", "Josane", "F", "Sousa", "-", "jdfsousa@gmail.com;", "Enilza", "M", "Espreafico*", "-", "emesprea@fmrp.usp.br", "*", "Corresponding", "author", "Published:", "22", "January", "2008", "BMC", "Cancer", "2008,", "8:19", "doi:10.1186/1471-2407-8-19", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2407/8/19", "Received:", "17", "July", "2007", "Accepted:", "22", "January", "2008", "©", "2008", "Sousa", "and", "Espreafico;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Melanoma", "progression", "occurs", "through", "three", "major", "stages:", "radial", "growth", "phase", "(RGP),", "confined", "to", "the", "epidermis;", "vertical", "growth", "phase", "(VGP),", "when", "the", "tumor", "has", "invaded", "into", "the", "dermis;", "and", "metastasis.", "In", "this", "work,", "we", "used", "suppression", "subtractive", "hybridization", "(SSH)", "to", "investigate", "the", "molecular", "signature", "of", "melanoma", "progression,", "by", "comparing", "a", "group", "of", "metastatic", "cell", "lines", "with", "an", "RGP-like", "cell", "line", "showing", "characteristics", "of", "early", "neoplastic", "lesions", "including", "expression", "of", "the", "metastasis", "suppressor", "KISS1,", "lack", "of", "αvβ3-integrin", "and", "low", "levels", "of", "RHOC.", "Methods:", "Two", "subtracted", "cDNA", "collections", "were", "obtained,", "one", "(RGP", "library)", "by", "subtracting", "the", "RGP", "cell", "line", "(WM1552C)", "cDNA", "from", "a", "cDNA", "pool", "from", "four", "metastatic", "cell", "lines", "(WM9,", "WM852,", "1205Lu", "and", "WM1617),", "and", "the", "other", "(Met", "library)", "by", "the", "reverse", "subtraction.", "Clones", "were", "sequenced", "and", "annotated,", "and", "expression", "validation", "was", "done", "by", "Northern", "blot", "and", "RT-PCR.", "Gene", "Ontology", "annotation", "and", "searches", "in", "large-scale", "melanoma", "expression", "studies", "were", "done", "for", "the", "genes", "identified.", "Results:", "We", "identified", "367", "clones", "from", "the", "RGP", "library", "and", "386", "from", "the", "Met", "library,", "of", "which", "351", "and", "368,", "respectively,", "match", "human", "mRNA", "sequences,", "representing", "288", "and", "217", "annotated", "genes.", "We", "confirmed", "the", "differential", "expression", "of", "all", "genes", "selected", "for", "validation.", "In", "the", "Met", "library,", "we", "found", "an", "enrichment", "of", "genes", "in", "the", "growth", "factors/receptor,", "adhesion", "and", "motility", "categories", "whereas", "in", "the", "RGP", "library,", "enriched", "categories", "were", "nucleotide", "biosynthesis,", "DNA", "packing/repair,", "and", "macromolecular/vesicular", "trafficking.", "Interestingly,", "19%", "of", "the", "genes", "from", "the", "RGP", "library", "map", "to", "chromosome", "1", "against", "4%", "of", "the", "ones", "from", "Met", "library.", "Conclusion:", "This", "study", "identifies", "two", "populations", "of", "genes", "differentially", "expressed", "between", "melanoma", "cell", "lines", "from", "two", "tumor", "stages", "and", "suggests", "that", "these", "sets", "of", "genes", "represent", "profiles", "of", "less", "aggressive", "versus", "metastatic", "melanomas.", "A", "search", "for", "expression", "profiles", "of", "melanoma", "in", "available", "expression", "study", "databases", "allowed", "us", "to", "point", "to", "a", "great", "potential", "of", "involvement", "in", "tumor", "progression", "for", "several", "of", "the", "genes", "identified", "here.", "A", "few", "sequences", "obtained", "here", "may", "also", "contribute", "to", "extend", "annotated", "mRNAs", "or", "to", "the", "identification", "of", "novel", "transcripts.", "Page", "1", "of", "18", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "JCB:", "ARTICLE", "Intracellular", "collagen", "degradation", "mediated", "by", "uPARAP/Endo180", "is", "a", "major", "pathway", "of", "extracellular", "matrix", "turnover", "during", "malignancy", "Alejandro", "C.", "Curino,1", "Lars", "H.", "Engelholm,4", "Susan", "S.", "Yamada,3", "Kenn", "Holmbeck,3", "Leif", "R.", "Lund,4", "Alfredo", "A.", "Molinolo,2", "Niels", "Behrendt,4", "Boye", "Schnack", "Nielsen,4", "and", "Thomas", "H.", "Bugge1", "1Proteases", "and", "Tissue", "Remodeling", "Unit", "and", "2Molecular", "Carcinogenesis", "Unit,", "Oral", "and", "Pharyngeal", "Cancer", "Branch,", "and", "3Matrix", "Metalloproteinase", "Unit,", "Craniofacial", "and", "Skeletal", "Diseases", "Branch,", "National", "Institute", "of", "Dental", "and", "Craniofacial", "Research,", "National", "Institutes", "of", "Health,", "Bethesda,", "MD", "20892", "4Finsen", "Laboratory,", "Rigshospitalet,", "DK-2100", "Copenhagen", "Ø,", "Denmark", "Y", "G", "O", "L", "O", "I", "B", "L", "L", "E", "C", "F", "O", "L", "A", "N", "R", "U", "O", "J", "E", "H", "T", "W", "e", "can", "recently", "mediate", "reported", "the", "cellular", "that", "uptake", "uPARAP/Endo180", "and", "lysoso-", "mal", "degradation", "of", "collagen", "by", "cultured", "fi-", "broblasts.", "Here,", "we", "show", "that", "uPARAP/Endo180", "has", "a", "key", "role", "in", "the", "degradation", "of", "collagen", "during", "mammary", "carcinoma", "progression.", "In", "the", "normal", "murine", "mammary", "gland,", "uPARAP/Endo180", "is", "widely", "expressed", "in", "periduc-", "tal", "fibroblast-like", "mesenchymal", "cells", "that", "line", "mammary", "epithelial", "cells.", "This", "pattern", "of", "uPARAP/Endo180", "expres-", "sion", "is", "preserved", "during", "polyomavirus", "middle", "T–induced", "Introduction", "Malignant", "progression", "is", "an", "example", "of", "a", "radical", "tissue", "remod-", "eling", "process", "in", "which", "one", "tissue", "(normal", "tissue)", "is", "invaded", "and", "is", "eventually", "completely", "substituted", "by", "a", "different", "tissue", "(tumor", "tissue).", "The", "process", "is", "characterized", "by", "dramatic", "increases", "in", "both", "the", "rate", "of", "synthesis", "and", "the", "rate", "of", "turnover", "of", "ECM", "com-", "ponents", "in", "a", "complex", "cycle", "of", "continuous", "ECM", "deposition", "and", "degradation.", "ECM", "degradation", "serves", "at", "least", "four", "different", "functions", "that", "all", "are", "essential", "to", "tumor", "progression.", "It", "facilitates", "the", "physical", "expansion", "of", "the", "tumor", "mass,", "liberates", "latent", "tumor", "growth", "factors", "embedded", "within", "the", "ECM,", "enables", "the", "forma-", "tion", "of", "a", "neovasculature", "within", "the", "expanding", "tumor", "mass,", "and", "subverts", "the", "proliferative", "restrictions", "imposed", "on", "tumor", "cells", "by", "ECM", "(Hotary", "et", "al.,", "2003;", "Mott", "and", "Werb,", "2004).", "Inhibition", "of", "ECM", "degradation", "has,", "therefore,", "long", "been", "recognized", "as", "an", "attractive", "target", "for", "therapeutic", "intervention", "aimed", "at", "limiting", "tumor", "growth", "(Coussens", "and", "Werb,", "2002).", "The", "degradation", "of", "ECM", "during", "malignant", "progression", "is", "a", "proteolytic", "event.", "Because", "most", "tumor", "cell", "lines", "produce", "in-", "creased", "levels", "of", "proteases,", "ECM", "degradation", "was", "initially", "believed", "to", "be", "a", "relatively", "simple", "process", "that", "was", "executed", "Correspondence", "to", "Thomas", "H.", "Bugge:", "thomas.bugge@nih.gov", "Abbreviation", "used", "in", "this", "paper:", "PymT;", "polyomavirus", "middle", "T.", "The", "Journal", "of", "Cell", "Biology,", "Vol.", "169,", "No.", "6,", "June", "20,", "2005", "977–985", "http://www.jcb.org/cgi/doi/10.1083/jcb.200411153", "mammary", "carcinogenesis,", "with", "strong", "uPARAP/Endo180", "expression", "by", "mesenchymal", "cells", "embedded", "within", "the", "col-", "lagenous", "stroma", "surrounding", "nests", "of", "uPARAP/Endo180-", "negative", "tumor", "cells.", "Genetic", "ablation", "of", "uPARAP/", "Endo180", "impaired", "collagen", "turnover", "that", "is", "critical", "to", "tu-", "mor", "expansion,", "as", "evidenced", "by", "the", "abrogation", "of", "cellular", "collagen", "uptake,", "tumor", "fibrosis,", "and", "blunted", "tumor", "growth.", "These", "studies", "identify", "uPARAP/Endo180", "as", "a", "key", "mediator", "of", "collagen", "turnover", "in", "a", "pathophysiological", "context.", "directly", "by", "tumor", "cells", "through", "the", "secretion", "of", "an", "assortment", "of", "ECM-degrading", "proteases", "(Liotta", "et", "al.,", "1980,", "1991;", "Danø", "et", "al.,", "1985).", "However,", "an", "exhaustive", "body", "of", "work", "that", "now", "spans", "more", "than", "two", "decades", "has", "demonstrated", "a", "much", "higher", "level", "of", "complexity.", "Thus,", "the", "current", "paradigm", "holds", "that", "ECM", "degradation", "during", "malignant", "progression", "is", "the", "result", "of", "a", "finely", "coordinated", "interplay", "between", "tumor", "cells,", "tumor-", "associated", "stromal", "cells,", "and", "tumor-infiltrating", "inflammatory", "cells,", "each", "having", "distinct", "and", "indispensable", "roles", "in", "the", "pro-", "cess.", "Furthermore,", "this", "work", "has", "identified", "the", "tumor", "stromal", "cell", "as", "one", "of", "the", "principle", "mediators", "of", "ECM", "turnover", "during", "tumor", "invasion.", "As", "such,", "malignant", "progression", "may", "show", "striking", "similarities", "to", "a", "variety", "of", "normal", "physiological", "tissue", "remodeling", "processes", "(Danø", "et", "al.,", "1999;", "Werb", "et", "al.,", "1999;", "Liotta", "and", "Kohn,", "2001).", "Collagens", "are", "the", "most", "abundant", "ECM", "components", "in", "the", "body", "and", "are", "a", "universal", "part", "of", "the", "tumor", "ECM", "(Hanahan", "and", "Weinberg,", "2000;", "Liotta", "and", "Kohn,", "2001;", "Chambers", "et", "al.,", "2002).", "They", "consist", "of", "three", "polypeptide", "chains,", "each", "with", "a", "single,", "long", "uninterrupted", "section", "of", "Gly-X-Y", "repeats", "that", "are", "intertwined", "to", "produce", "a", "superhelix", "that", "buries", "the", "peptide", "bonds", "within", "the", "interior", "of", "the", "helix.", "The", "fibrillar", "collagens", "spontaneously", "self", "associate", "to", "form", "fibrils", "that", "range", "in", "diameter", "JCB", "977" ]

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[ "Clinical", "science", "Department", "of", "Ophthalmology,", "Medical", "University", "of", "Vienna,", "Austria", "Correspondence", "to", "Clemens", "Vass,", "Department", "of", "Ophthalmology", "and", "Optometry,", "Medical", "University", "of", "Vienna,", "General", "Hospital,", "W¨ahringer", "G¨urtel", "18-20,", "A-1090", "Vienna,", "Austria;", "clemens.vass@", "meduniwien.ac.at", "Accepted", "3", "July", "2010", "Published", "Online", "First", "30", "August", "2010", "This", "paper", "is", "freely", "available", "online", "under", "the", "BMJ", "Journals", "unlocked", "scheme,", "see", "http://", "bjo.bmj.com/site/about/", "unlocked.xhtml", "680", "Position", "of", "retinal", "blood", "vessels", "correlates", "with", "retinal", "nerve", "fibre", "layer", "thickness", "profiles", "as", "measured", "with", "GDx", "VCC", "and", "ECC", "Hemma", "Resch,", "Barbara", "Brela,", "Christa", "Resch-Wolfslehner,", "Clemens", "Vass", "ABSTRACT", "Aim", "To", "evaluate", "the", "correlation", "of", "the", "retinal", "blood", "vessel", "position", "and", "the", "retinal", "nerve", "fibre", "layer", "(RNFL)", "thickness", "profile.", "Methods", "RNFL", "thickness", "of", "81", "healthy", "subjects", "was", "measured", "using", "scanning", "laser", "polarimetry", "(SLP).", "To", "quantify", "the", "retinal", "blood", "vessel", "position,", "the", "angle", "(superior", "and", "inferior)", "between", "a", "horizontal", "line", "and", "a", "line", "from", "the", "optic", "disc", "centre", "to", "the", "intersection", "of", "the", "most", "temporal", "major", "retinal", "blood", "vessel", "and", "the", "outer", "margin", "of", "the", "measurement", "ellipse", "was", "measured", "on", "the", "SLP", "printout.", "Results", "A", "negative", "correlation", "was", "found", "between", "both", "the", "superior", "and", "inferior", "angle", "and", "the", "superotemporal", "and", "inferotemporal", "RNFL", "thickness,", "and", "a", "positive", "correlation", "between", "both", "angles", "and", "the", "superonasal", "and", "inferonasal", "RFNL", "thickness.", "The", "steepest", "slope", "of", "the", "regression", "line", "was", "located", "in", "the", "superotemporal", "and", "inferotemporal", "regions", "(", "0.7", "to", "1.0", "mm/8).", "Using", "this", "slope,", "the", "difference", "in", "RNFL", "thickness", "for", "the", "interquartile", "range", "of", "the", "superior", "angle", "was", "13", "mm.", "Conclusion", "RNFL", "thickness", "profiles", "correlate", "with", "the", "location", "of", "the", "main", "temporal", "superior", "and", "inferior", "blood", "vessels.", "The", "application", "of", "a", "normative", "database,", "taking", "into", "account", "the", "position", "of", "major", "blood", "vessels,", "might", "improve", "the", "diagnostic", "power", "of", "RNFL", "measurement.", "INTRODUCTION", "The", "GDx", "(Carl", "Zeiss", "Meditec,", "Dublin,", "Califonia,", "USA)", "is", "a", "scanning", "laser", "polarimeter", "that", "assesses", "retinal", "nerve", "fibre", "layer", "(RNFL)", "thickness", "in", "the", "peripapillary", "retina", "and", "discriminates", "well", "between", "normal", "subjects", "and", "patients", "with", "glaucoma.1e4", "In", "healthy", "eyes,", "the", "peripapillary", "RNFL", "thickness", "modulation", "pattern", "around", "the", "optic", "disc,", "also", "referred", "to", "as", "a", "temporalesuperiore", "nasaleinferioretemporal", "(TSNIT)", "graph,", "was", "shown", "to", "follow", "a", "double-hump", "pattern,", "with", "thicker", "RNFL", "superiorly", "and", "inferiorly", "and", "thinner", "RNFL", "temporally", "and", "nasally.5", "Considerable", "inter-", "individual", "variability", "in", "RNFL", "thickness", "values", "among", "normal", "subjects", "as", "measured", "with", "optical", "coherence", "tomography", "(OCT),6", "and", "some", "overlap", "in", "thickness", "values", "between", "normal", "subjects", "and", "patients", "with", "glaucoma", "have", "been", "reported", "in", "several", "studies", "conducted", "by", "scanning", "laser", "polarimetry", "(SLP).2e4", "7", "8", "Various", "diseases,", "most", "notably", "glaucoma,", "result", "in", "the", "death", "of", "retinal", "ganglion", "cells", "(RGCs)", "and", "the", "degeneration", "of", "their", "axons.", "The", "loss", "of", "RGC", "axons", "in", "turn", "leads", "to", "a", "thinning", "of", "the", "RNFL.", "One", "method", "for", "assessing", "pathological", "RNFL", "appear-", "ance", "is", "by", "comparing", "the", "RNFL", "with", "normative", "values,", "derived", "from", "healthy", "subjects.", "These", "normative", "values", "will", "be", "more", "specific", "when", "normal", "physiological", "differences", "are", "taken", "into", "account.", "Only", "recently,", "Hood", "et", "al", "have", "demonstrated", "qualitatively", "that", "the", "local", "maxima", "in", "the", "RNFL", "profile", "of", "OCT", "and", "GDx", "are", "associated", "with", "blood", "vessels.9", "10", "Statistical", "analyses", "concerning", "the", "impact", "of", "retinal", "blood", "vessel", "position", "on", "the", "total", "circum-", "papillary", "TSNIT", "profile", "of", "RNFL", "have", "not", "yet", "been", "published.", "Understanding", "the", "sources", "of", "the", "inter-", "subject", "variability", "is", "central", "to", "the", "understanding", "and", "improvement", "of", "RNFL", "thickness", "measure-", "ments", "as", "a", "test", "for", "glaucomatous", "damage.", "It", "was", "the", "aim", "of", "the", "present", "study", "to", "examine", "the", "influ-", "ence", "of", "the", "retinal", "blood", "vessel", "position", "on", "the", "RNFL", "thickness", "profile", "around", "the", "optic", "disc", "as", "measured", "with", "GDx", "VCC", "(variable", "corneal", "compensation)", "and", "ECC", "(enhanced", "corneal", "compensation).", "SUBJECTS", "AND", "METHODS", "Subjects", "The", "study", "protocol", "was", "approved", "by", "the", "Ethics", "Committee", "of", "the", "Medical", "University", "of", "Vienna", "and", "followed", "the", "guidelines", "of", "Good", "Clinical", "Prac-", "tice", "and", "the", "Declaration", "of", "Helsinki.", "A", "total", "of", "83", "subjects", "of", "both", "sexes", "aged", "between", "19", "and", "71", "years", "(mean", "27.27", "years,", "6", "9.5)", "were", "included.", "Inclusion", "and", "exclusion", "criteria", "Inclusion", "criteria", "were", "normal", "ophthalmic", "findings,", "especially", "normal", "appearance", "of", "the", "optic", "disc,", "normal", "visual", "fields", "and", "intraocular", "pressure", "(IOP),", "and", "lack", "of", "significant", "retinal", "disorder.", "An", "abnormal", "visual", "field", "was", "defined", "as", "a", "glaucoma", "hemifield", "test", "outside", "normal", "limits", "and/or", "a", "corrected", "pattern", "standard", "deviation", "with", "p", "<0.05.11", "A", "normal", "IOP", "was", "defined", "as", "#21", "mm", "Hg.", "Any", "of", "the", "following", "excluded", "a", "subject", "from", "participation", "in", "the", "trial:", "evidence", "of", "any", "eye", "disease", "except", "refractive", "error,", "history", "of", "ocular", "trauma", "or", "intraocular", "surgery", "within", "the", "last", "6", "months,", "ocular", "inflammation", "or", "infection", "within", "the", "last", "3", "months,", "astigmatism", "more", "than", "+2.0", "dioptres", "and", "ametropia", "of", "more", "than", "65.0", "dioptres.", "Experimental", "paradigm", "Initially", "a", "prestudy", "screening", "was", "carried", "out,", "where", "the", "medical", "and", "ocular", "history", "was", "taken.", "A", "complete", "ophthalmological", "examination", "was", "performed,", "including", "fundoscopy,", "visual", "acuity,", "Br", "J", "Ophthalmol", "2011;95:680e684.", "doi:10.1136/bjo.2009.170068" ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Environmental", "and", "Public", "Health", "Volume", "2009,", "Article", "ID", "969764,", "7", "pages", "doi:10.1155/2009/969764", "Clinical", "Study", "Child", "Skeletal", "Fluorosis", "from", "Indoor", "Burning", "of", "Coal", "in", "Southwestern", "China", "Xianghui", "Qin,1", "Shouying", "Wang,1", "Maojuan", "Yu,1", "Lei", "Zhang,2", "Xinhua", "Li,1", "Zhen", "Zuo,1", "Xiuhui", "Zhang,1", "and", "Lihua", "Wang1", "1", "Department", "of", "Preventive", "Medicine,", "Guiyang", "Medical", "College,", "School", "of", "Public", "Health,", "Guiyang,", "Guizhou", "550004,", "China", "2", "Office", "of", "Health", "Data", "and", "Research,", "Mississippi", "State", "Department", "of", "Health,", "P.", "O.", "Box", "1700,", "Jackson,", "MS", "39215-1700,", "USA", "Correspondence", "should", "be", "addressed", "to", "Maojuan", "Yu,", "maojuanyu@gmc.edu.cn", "Received", "14", "November", "2008;", "Revised", "8", "March", "2009;", "Accepted", "12", "August", "2009", "Recommended", "by", "Stuart", "Batterman", "Objectives.", "We", "assess", "the", "prevalence", "and", "pathogenic", "stage", "of", "skeletal", "fluorosis", "among", "children", "and", "adolescents", "residing", "in", "a", "severe", "coal-burning", "endemic", "fluorosis", "area", "of", "southwest", "China.", "Methods.", "We", "used", "a", "cross-sectional", "design.", "A", "total", "of", "1,616", "students", "aged", "between", "7", "and", "16", "years", "in", "Zhijin", "County,", "Guizhou,", "China", "in", "late", "2004", "were", "selected", "via", "a", "cluster", "sampling", "of", "all", "9-year", "compulsory", "education", "schools", "to", "complete", "the", "study", "questionnaire.", "Any", "student", "lived", "in", "a", "household", "that", "burned", "coal,", "used", "an", "open-burning", "stove,", "or", "baked", "foodstuffs", "over", "a", "coal", "stove", "was", "deemed", "high-risk", "for", "skeletal", "fluorosis.", "About", "23%", "(370)", "of", "students", "(188", "boys,", "182", "girls)", "were", "identified", "as", "high-risk", "and", "further", "examined", "by", "X-ray.", "Results.", "One-third", "of", "the", "370", "high-risk", "participants", "were", "diagnosed", "with", "skeletal", "fluorosis.", "Overall", "prevalence", "of", "child", "skeletal", "fluorosis", "due", "to", "indoor", "burning", "of", "coal", "was", "7.5%.", "Children", "aged", "12–16", "years", "were", "significantly", "more", "likely", "to", "be", "diagnosed", "with", "skeletal", "fluorosis", "than", "children", "aged", "7–11", "years", "(OR", "=", "1.84,", "95%", "CI:", "1.17–2.90;", "P", "=", ".0082).", "Four", "types", "of", "skeletal", "fluorosis", "were", "identified:", "constrictive", "(60.7%),", "raritas", "(15.6%),", "mixed", "(16.4%),", "and", "soft", "(7.4%).", "Most", "diagnosed", "cases", "(91%)", "were", "mild", "or", "moderate", "in", "severity.", "In", "addition,", "about", "97%", "of", "370", "high-risk", "children", "were", "identified", "with", "dental", "fluorosis.", "Dental", "fluorosis", "was", "highly", "correlated", "with", "skeletal", "fluorosis", "in", "this", "study.", "Conclusions.", "Skeletal", "fluorosis", "among", "children", "may", "contribute", "to", "poor", "health", "and", "reduced", "productivity", "when", "they", "reach", "adulthood.", "Further", "efforts", "to", "reduce", "fluoride", "exposure", "among", "children", "in", "southwestern", "of", "China", "where", "coal", "is", "burned", "indoors", "are", "desperately", "needed.", "Copyright", "©", "2009", "Xianghui", "Qin", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "1.", "Introduction", "Fluoride", "has", "both", "positive", "and", "negative", "effects", "on", "human", "health.", "In", "fact,", "fluoride", "has", "been", "shown", "to", "prevent", "dental", "caries", "mainly", "through", "fluoride’s", "topical", "action.", "Conversely,", "chronic", "exposure", "to", "excessive", "amounts", "of", "fluoride", "may", "cause", "an", "abnormal", "condition", "called", "skeletal", "fluorosis.", "Overexpo-", "sure", "to", "environmental", "fluoride", "has", "caused", "endemic", "fluorosis", "to", "become", "a", "major", "public", "health", "problem", "in", "China.", "Endemic", "fluorosis", "is", "prevalent", "in", "29", "provinces,", "municipalities,", "or", "autonomous", "regions", "in", "China", "and", "is", "associated", "with", "three", "types", "of", "fluoride", "exposure:", "contaminated", "drinking", "water,", "pollution", "from", "coal", "burning,", "and", "tea", "drinking.", "More", "than", "10", "million", "people", "in", "Guizhou", "Province", "suffer", "from", "various", "forms", "of", "fluorosis", "[1,", "2].", "In", "the", "southwestern", "province", "of", "Guizhou,", "endemic", "fluorosis", "has", "been", "attributed", "to", "the", "use", "of", "fluoride-rich", "coal", "as", "an", "indoor", "fuel", "source", "[1–6].", "Coal", "is", "the", "main", "fuel", "used", "by", "the", "local", "inhabitants", "of", "Zhijin", "County.", "Zhijin", "is", "a", "mountainous", "area", "where", "the", "moist", "climate", "requires", "residents", "to", "burn", "coal", "stoves", "year", "round", "in", "order", "to", "dry", "corn,", "a", "dietary", "staple.", "Similar", "to", "other", "peasants", "in", "this", "region", "of", "China,", "the", "local", "inhabitants", "use", "open-burning", "style", "stoves,", "without", "adequate", "ventilation,", "to", "bake", "food", "or", "dry", "corn", "hanging", "over", "the", "stove.", "Fluoride", "is", "released", "from", "the", "coal", "and", "accumulates", "in", "the", "drying", "corn,", "significantly", "increasing", "the", "amount", "of", "fluoride", "a", "family", "member", "is", 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[ "HAND", "(2009)", "4:108–112", "DOI", "10.1007/s11552-008-9153-8", "ORIGINAL", "PAPER", "Hammering", "K-wires", "is", "Superior", "to", "Drilling", "with", "Irrigation", "Bas", "B.", "G.", "M.", "Franssen", "&", "Arnold", "H.", "Schuurman", "&", "Pascal", "C.", "R.", "Brouha", "&", "Moshe", "Kon", "Received:", "28", "September", "2008", "/", "Accepted:", "14", "November", "2008", "/", "Published", "online:", "10", "December", "2008", "#", "The", "Author(s)", "2008.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Cooling", "during", "drilling", "Kirschner", "wires", "is", "not", "always", "effective", "in", "preventing", "thermal", "related", "damage.", "In", "this", "study,", "we", "used", "a", "human", "in", "vitro", "model", "and", "compared", "temperature", "elevation,", "insertion", "time,", "and", "extraction", "force", "between", "three", "Kirschner", "wire", "insertion", "methods—drilling", "with", "and", "without", "irrigation", "and", "pneumatic", "hammering.", "Forty", "five", "Kirschner", "wires", "were", "inserted", "into", "15", "fresh", "human", "cadaver", "metacarpals.", "All", "three", "insertion", "methods", "were", "applied", "in", "each", "metacarpal.", "Drilling", "without", "irrigation", "resulted", "in", "a", "temperature", "elevation", "of", "67.25", "±", "5.4", "ºC", "with", "significantly", "lower", "values", "for", "drilling", "with", "irrigation", "(4.15", "±", "0.6", "ºC)", "and", "pneumatic", "hammering", "(31.52", "±", "3.4", "ºC).", "The", "insertion", "time", "for", "pneumatic", "hammering", "(47.63", "±", "8.8", "s)", "was", "significantly", "lower", "compared", "to", "drilling", "without", "irrigation", "(263.16", "±", "36.5", "s)", "and", "drilling", "with", "irrigation", "(196.10", "±", "28.5", "s).", "Extraction", "forces", "after", "drilling", "without", "irrigation,", "drilling", "with", "irrigation,", "and", "pneumatic", "hammer-", "ing", "were", "39.85", "±", "4.1", "N,", "57.81", "±", "6.5", "N,", "and", "62.23", "±", "6.7", "N,", "respectively.", "Pneumatic", "hammering", "is", "superior", "to", "drilling", "without", "irrigation,", "especially", "when", "irrigation", "is", "not", "possible.", "Keywords", "Drilling", ".", "Metacarpal", ".", "Pneumatic", "hammer", ".", "Irrigation", ".", "K-wire", "B.", "B.", "G.", "M.", "Franssen", "(*)", ":", "A.", "H.", "Schuurman", ":", "P.", "C.", "R.", "Brouha", ":", "M.", "Kon", "Department", "of", "Plastic", "Reconstructive", "and", "Hand", "Surgery,", "University", "Medical", "Center", "Utrecht,", "Room", "number", "G.04.122,", "P.O.", "Box", "85500,", "3508", "GA", "Utrecht,", "The", "Netherlands", "e-mail:", "bbgmfranssen@gmail.com", "Introduction", "Kirschner", "wires", "(K-wires)", "are", "often", "used", "in", "hand", "surgery", "because", "it", "is", "a", "quick", "and", "simple", "method", "for", "stabilization", "of", "fractures", "[19].", "Multiple", "passes,", "type", "of", "K-wire", "configuration,", "quality", "of", "soft", "tissues,", "and", "accuracy", "of", "placement", "are", "important", "issues", "in", "K-wire", "fixation.", "The", "drilling", "technique", "itself", "may", "play", "an", "important", "role", "in", "the", "occurrence", "of", "frictional-heat-related", "complications", "like", "necrotic", "bone", "around", "the", "wires", "[8,", "12].", "This", "predisposes", "to", "pin–track", "infections", "and", "loosening", "of", "K-wires", "which", "can", "result", "in", "early", "removal", "or", "even", "osteomyelitis", "[3,", "16].", "Thermal", "necrosis", "is", "a", "product", "of", "time", "[4,", "6]", "temperature", "[2,", "7],", "drill", "speed", "[4,", "21],", "insertion", "force", "[1,", "20],", "K-wire", "characteristics", "[13,", "18],", "and", "the", "factor", "irrigation", "[14,", "24].", "The", "influence", "of", "heat", "generation", "on", "bone", "has", "long", "been", "recognized.", "Hippocrates", "(500", "BC)", "even", "recommended", "that", "the", "trepanning", "tool", "must", "be", "cooled", "during", "bone", "removal", "to", "avoid", "injury", "to", "the", "surrounding", "bone", "[17].", "Temperature", "elevation", "during", "drilling", "into", "bone", "is", "nowadays", "kept", "to", "a", "minimum", "by", "external", "or", "more", "effectively", "by", "internal", "irrigating", "[15,", "24].", "Internal", "irrigation", "however", "is", "not", "useful", "when", "drilling", "K-wires,", "because", "it", "is", "not", "possible", "to", "let", "the", "cooling", "agent", "passing", "down", "the", "center", "of", "the", "K-wire", "[14].", "Therefore,", "the", "external", "irrigation", "technique", "must", "be", "used.", "This", "technique", "is", "effective", "when", "a", "constant", "flow", "is", "provided", "at", "the", "point", "of", "insertion.", "In", "areas", "of", "limited", "access,", "however,", "this", "can", "not", "be", "realized", "and", "therefore", "will", "result", "in", "less", "or", "no", "cooling", "effect", "at", "all", "[15,", "22,", "24].", "Also,", "constant", "external", "irrigation", "at", "the", "opposite", "cortex", "or", "during", "percutaneous", "drilling", "is", "usually", "impossible,", "resulting", "in", "a", "very", "low", "or", "absent", "cooling", "effect", "[9].", "The", "ultimate", "K-wire", "insertion", "method", "would", "be", "a", "technique", "without", "the", "necessity", "of", "irrigation", "but", "with", "the", "advantages", "of", "drilling", "and", "without", "thermal", "related", "compli-" ]

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[ "Int", "J", "Emerg", "Med", "(2010)", "3:271–278", "DOI", "10.1007/s12245-010-0214-8", "ORIGINAL", "RESEARCH", "ARTICLE", "Perceptions", "of", "nurse", "practitioners", "by", "emergency", "department", "doctors", "in", "Australia", "Tracey", "J.", "Weiland", "&", "Claire", "Mackinlay", "&", "George", "A.", "Jelinek", "Received:", "22", "December", "2009", "/", "Accepted:", "24", "June", "2010", "/", "Published", "online:", "26", "August", "2010", "#", "Springer-Verlag", "London", "Ltd", "2010", "Abstract", "Background", "The", "Australian", "Medical", "Association", "is", "strong-", "ly", "opposed", "to", "the", "nurse", "practitioner", "(NP)", "role", "with", "concerns", "that", "NPs", "may", "become", "doctor", "substitutes", "without", "the", "requisite", "training", "and", "education", "that", "the", "medical", "role", "demands.", "Despite", "this,", "NPs", "have", "been", "heralded", "by", "some", "as", "a", "potential", "solution", "to", "the", "access", "block,", "workforce", "shortage", "and", "increased", "demand", "affecting", "emergency", "depart-", "ments", "(EDs).", "Aims", "The", "purpose", "of", "this", "study", "was", "to", "determine", "the", "perception", "of", "NPs", "by", "medical", "staff", "working", "in", "Australian", "EDs.", "Methods", "Semi-structured", "telephone", "interviews", "were", "con-", "ducted", "with", "closed", "and", "open-ended", "questions.", "Participants", "were", "drawn", "from", "a", "representative", "stratified", "sample", "of", "two", "city,", "two", "metropolitan", "and", "two", "provincial", "hospitals", "of", "each", "State/Territory.", "Results", "A", "total", "of", "95", "doctors", "from", "35", "EDs", "participated", "in", "this", "study", "including", "36", "Departmental", "Directors;", "36%", "of", "participating", "Directors", "indicated", "having", "an", "NP", "on", "staff.", "The", "views", "expressed", "in", "this", "paper", "are", "those", "of", "the", "author(s)", "and", "not", "those", "of", "the", "editors,", "editorial", "board", "or", "publisher.", "Electronic", "supplementary", "material", "The", "online", "version", "of", "this", "article", "(doi:10.1007/s12245-010-0214-8)", "contains", "supplementary", "material,", "which", "is", "available", "to", "authorized", "users.", "T.", "J.", "Weiland", "(*)", ":", "C.", "Mackinlay", ":", "G.", "A.", "Jelinek", "Emergency", "Practice", "Innovation", "Centre,", "St.", "Vincent’s", "Hospital", "Melbourne,", "P.O.", "Box", "2900,", "Fitzroy,", "Melbourne,", "Australia", "e-mail:", "Tracey.Weiland@svhm.or.au", "T.", "J.", "Weiland", ":", "G.", "A.", "Jelinek", "Department", "of", "Medicine,", "The", "University", "of", "Melbourne,", "Melbourne,", "Australia", "Doctors", "were", "strongly", "opposed", "to", "the", "statement", "that", "NPs", "could", "replace", "either", "nurses", "or", "other", "prevocational", "doctors;", "71", "interviewees", "commented", "on", "the", "role", "of", "NPs", "in", "the", "ED.", "Thematic", "analyses", "revealed", "polarised", "views", "held", "by", "doctors.", "Eight", "major", "themes", "were", "identified,", "the", "most", "common", "being", "that", "there", "is", "a", "lack", "of", "clarity", "of", "the", "NP", "role", "definition,", "their", "scope", "of", "practice", "and", "differentiation", "from", "the", "medical", "role.", "Conclusion", "Although", "ED", "NPs", "represent", "a", "highly", "skilled", "professional", "group", "their", "role", "is", "poorly", "understood", "by", "ED", "doctors.", "Opposition", "to", "the", "NP", "role", "is", "a", "significant", "barrier", "to", "the", "introduction", "of", "great", "numbers", "of", "ED", "NPs", "as", "a", "strategy", "to", "overcome", "the", "medical", "workforce", "shortage.", "Keywords", "Nurse", "practitioner", ".", "Intern", ".", "Emergency", "medicine", ".", "Supervision", "Introduction", "The", "Australian", "Medical", "Association", "is", "strongly", "opposed", "to", "the", "nurse", "practitioner", "(NP)", "role", "with", "concerns", "that", "NPs", "may", "become", "doctor", "substitutes", "without", "the", "requisite", "training", "and", "education", "that", "the", "medical", "role", "demands", "[1,", "2].", "Despite", "this,", "NPs", "have", "been", "heralded", "by", "some", "as", "a", "potential", "solution", "to", "the", "access", "block,", "workforce", "shortage", "and", "increased", "demand", "affecting", "emergency", "departments", "(EDs)", "[3].", "This", "view", "is", "reflected", "in", "government", "with", "increased", "funding", "for", "NPs", "at", "Federal", "[4]", "and", "State", "levels,", "with", "some", "Australian", "State", "Governments", "releasing", "funding", "to", "increase", "NP", "numbers", "within", "EDs", "[5,", "6].", "Further", "support", "for", "NPs", "has", "come", "though", "the", "recent", "introduction", "of", "independent", "prescribing", "rights", "[7].", "Data", "regarding", "the", "impact", "of", "NPs", "within", "emergency", "medicine", "(EM)", "suggest", "a", "positive", "benefit", "on", "key", "perfor-" ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "(E)-1-(4-Bromophenyl)-2-(4-tert-butyl-", "phenyl)-1-phenylethene", "Chul-Bae", "Kim,a", "Chul-Hee", "Cho,a", "Kyu", "Yun", "Chaib", "and", "Kwangyong", "Parka*", "aSchool", "of", "Chemical", "Engineering", "and", "Materials", "Science,", "Chung-Ang", "University,", "Seoul", "156-756,", "South", "Korea,", "and", "bDepartment", "of", "Bionanochemistry,", "Wonkwang", "University,", "Iksan,", "Chonbuk", "570-749,", "South", "Korea", "Correspondence", "e-mail:", "kypark@cau.ac.kr", "Received", "11", "December", "2007;", "accepted", "10", "January", "2008", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "296", "K;", "mean", "(C–C)", "=", "0.006", "A˚;", "disorder", "in", "main", "residue;", "R", "factor", "=", "0.052;", "wR", "factor", "=", "0.177;", "data-to-parameter", "ratio", "=", "15.5.", "In", "the", "structure", "of", "the", "title", "compound,", "C24H23Br,", "the", "configuration", "about", "the", "double", "bond", "is", "E.", "The", "dihedral", "angles", "between", "the", "tert-butyl-substituted", "benzene", "ring", "and", "the", "unsubstituted", "and", "Br-substituted", "rings", "are", "57.1", "(2)", "and", "78.2", "(2)", ",", "respectively.", "The", "methyl", "groups", "are", "disordered", "over", "two", "positions;", "the", "site", "occupancy", "factors", "are", "ca", "0.8", "and", "0.2.", "Related", "literature", "For", "background,", "see:", "Mooney", "et", "al.", "(1984),", "Kraft", "et", "al.", "(1998),", "and", "Martin", "&", "Diederich", "(1999).", "For", "related", "structures,", "see:", "Gao", "et", "al.", "(2006),", "De", "Borger", "et", "al.", "(2005),", "Ogawa", "et", "al.", "(1992);", "Barnes", "&", "Chudek", "(2002);", "SethuSankar", "et", "al.", "(2003).", "organic", "compounds", "Experimental", "Crystal", "data", "C24H23Br", "Mr", "=", "391.33", "Triclinic,", "P1", "a", "=", "8.2950", "(4)", "A˚", "b", "=", "10.8173", "(5)", "A˚", "c", "=", "13.0447", "(6)", "A˚", "=", "112.415", "(3)", "=", "94.570", "(3)", "Data", "collection", "Bruker", "SMART", "CCD", "area-detector", "diffractometer", "Absorption", "correction:", "multi-scan", "(SADABS;", "Sheldrick,", "1996)", "Tmin", "=", "0.413,", "Tmax", "=", "0.923", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.051", "wR(F", "2)", "=", "0.177", "S", "=", "1.03", "4046", "reflections", "261", "parameters", "=", "105.402", "(3)", "V", "=", "1021.47", "(8)", "A˚", "3", "Z", "=", "2", "Mo", "K", "radiation", "=", "2.02", "mm", "1", "T", "=", "296", "(2)", "K", "0.45", "0.40", "0.04", "mm", "17917", "measured", "reflections", "4046", "independent", "reflections", "2070", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.052", "9", "restraints", "H-atom", "parameters", "constrained", "max", "=", "0.47", "e", "A˚", "3", "min", "=", "0.40", "e", "A˚", "3", "Data", "collection:", "SMART", "(Bruker,", "1998);", "cell", "refinement:", "SAINT", "(Bruker,", "1998);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEP-3", "(Farrugia,", "1997);", "software", "used", "to", "prepare", "material", "for", "publication:", "SHELXTL", "(Sheldrick,", "2008).", "We", "thank", "CMDS", "and", "Dr", "Junseong", "Lee", "of", "KAIST", "for", "use", "of", "the", "X-ray", "single-crystal", "diffractometer.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "TK2234).", "References", "Barnes,", "J.", "C.", "&", "Chudek,", "J.", "A.", "(2002).", "Acta", "Cryst.", "E58,", "o703–o705.", "Bruker", "(1998).", "SMART", "and", "SAINT.", "Version", "5.0.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "De", "Borger,", "R.,", "Vande", "Velde,", "C.", "M.", "L.", "&", "Blockhuys,", "F.", "(2005).", "Acta", "Cryst.", "E61,", "o819–o821.", "Farrugia,", "L.", "J.", "(1997).", "J.", "Appl.", "Cryst.", "30,", "565.", "Gao,", "L.,", "Peng,", "H.", "&", "He,", "H.-W.", "(2006).", "Acta", "Cryst.", "E62,", "o5032–o5033.", "Kraft,", "A.,", "Grimsdale,", "A.", "C.", "&", "Holmes,", "A.", "B.", "(1998).", "Angew.", "Chem.", "Int.", "Ed.", "37,", "402–428.", "Martin,", "R.", "E.", "&", "Diederich,", "F.", "(1999).", "Angew.", "Chem.", "Int.", "Ed.", "38,", "1350–1377.", "Mooney,", "W.", "F.", "III,", "Brown,", "P.", "E.,", "Russell,", "J.", "C.,", "Costa,", "S.", "B.,", "Pedersen,", "L.", "G.", "&", "Whitten,", "D.", "G.", "(1984).", "J.", "Am.", "Chem.", "Soc.", "106,", "5659–5667.", "Ogawa,", "K.,", "Sabo,", "T.,", "Yoshimura,", "S.,", "Takeuchi,", "Y.", "&", "Toriumi,", "K.", "(1992).", "J.", "Am.", "Chem.", "Soc.", "114,", "1041–1051.", "SethuSankar,", "K.,", "Saravanan,", "S.,", "Velmurugan,", "D.", "&", "Parvez,", "M.", "(2003).", "Acta", "Cryst.", "C59,", "o156–o158.", "Sheldrick,", "G.", "M.", "(1996).", "SADABS.", "University", "of", "Go¨", "ttingen,", "Germany.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Acta", "Cryst.", "(2008).", "E64,", "o457", "doi:10.1107/S1600536808000998", "Kim", "et", "al.", "o457" ]

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[ "Essential", "Role", "of", "RAB27A", "in", "Determining", "Constitutive", "Human", "Skin", "Color", "Yasuko", "Yoshida-Amano", "1", ",", "Akira", "Hachiya1*,", "Atsushi", "Ohuchi1,", "Gary", "P.", "Kobinger2,", "Takashi", "Kitahara1,", "Yoshinori", "Takema", "3", ",", "Mitsunori", "Fukuda4", "1", "Biological", "Science", "Laboratories,", "Kao", "Corporation,", "Haga,", "Tochigi,", "Japan,", "2", "Special", "Pathogens", "Program,", "National", "Microbiology", "Laboratory,", "Department", "of", "Medical", "Microbiology,", "Public", "Health", "Agency", "of", "Canada,", "University", "of", "Manitoba,", "Winnipeg,", "Manitoba,", "Canada,", "3", "Research", "and", "Development", "Global,", "Kao", "Corporation,", "Sumida-ku,", "Tokyo,", "Japan,", "4", "Laboratory", "of", "Membrane", "Trafficking", "Mechanisms,", "Department", "of", "Developmental", "Biology", "and", "Neurosciences,", "Graduate", "School", "of", "Life", "Sciences,", "Tohoku", "University,", "Sendai,", "Miyagi,", "Japan", "Abstract", "Human", "skin", "color", "is", "predominantly", "determined", "by", "melanin", "produced", "in", "melanosomes", "within", "melanocytes", "and", "subsequently", "distributed", "to", "keratinocytes.", "There", "are", "many", "studies", "that", "have", "proposed", "mechanisms", "underlying", "ethnic", "skin", "color", "variations,", "whereas", "the", "processes", "involved", "from", "melanin", "synthesis", "in", "melanocytes", "to", "the", "transfer", "of", "melanosomes", "to", "keratinocytes", "are", "common", "among", "humans.", "Apart", "from", "the", "activities", "in", "the", "melanogenic", "rate-limiting", "enzyme,", "tyrosinase,", "in", "melanocytes", "and", "the", "amounts", "and", "distribution", "patterns", "of", "melanosomes", "in", "keratinocytes,", "the", "abilities", "of", "the", "actin-", "associated", "factors", "in", "charge", "of", "melanosome", "transport", "within", "melanocytes", "also", "regulate", "pigmentation.", "Mutations", "in", "genes", "encoding", "melanosome", "transport-related", "molecules,", "such", "as", "MYO5A,", "RAB27A", "and", "SLAC-2A,", "have", "been", "reported", "to", "cause", "a", "human", "pigmentary", "disease", "known", "as", "Griscelli", "syndrome,", "which", "is", "associated", "with", "diluted", "skin", "and", "hair", "color.", "Thus", "we", "hypothesized", "that", "process", "might", "play", "a", "role", "in", "modulating", "skin", "color", "variations.", "To", "address", "that", "hypothesis,", "the", "correlations", "of", "expression", "of", "RAB27A", "and", "its", "specific", "effector,", "SLAC2-A,", "to", "melanogenic", "ability", "were", "evaluated", "in", "comparison", "with", "tyrosinase,", "using", "human", "melanocytes", "derived", "from", "19", "individuals", "of", "varying", "skin", "types.", "Following", "the", "finding", "of", "the", "highest", "correlation", "in", "RAB27A", "expression", "to", "the", "melanogenic", "ability,", "darkly-pigmented", "melanocytes", "with", "significantly", "higher", "RAB27A", "expression", "were", "found", "to", "transfer", "significantly", "more", "melanosomes", "to", "keratinocytes", "than", "lightly-pigmented", "melanocytes", "in", "co-culture", "and", "in", "human", "skin", "substitutes", "(HSSs)", "in", "vivo,", "resulting", "in", "darker", "skin", "color", "in", "concert", "with", "the", "difference", "observed", "in", "African-descent", "and", "Caucasian", "skins.", "Additionally,", "RAB27A", "knockdown", "by", "a", "lentivirus-derived", "shRNA", "in", "melanocytes", "concomitantly", "demonstrated", "a", "significantly", "reduced", "number", "of", "transferred", "melanosomes", "to", "keratinocytes", "in", "co-culture", "and", "a", "significantly", "diminished", "epidermal", "melanin", "content", "skin", "color", "intensity", "(DL*", "=", "4.4)", "in", "the", "HSSs.", "These", "data", "reveal", "the", "intrinsically", "essential", "role", "of", "RAB27A", "in", "human", "ethnic", "skin", "color", "determination", "and", "provide", "new", "insights", "for", "the", "fundamental", "understanding", "of", "regulatory", "mechanisms", "underlying", "skin", "pigmentation.", "Citation:", "Yoshida-Amano", "Y,", "Hachiya", "A,", "Ohuchi", "A,", "Kobinger", "GP,", "Kitahara", "T,", "et", "al.", "(2012)", "Essential", "Role", "of", "RAB27A", "in", "Determining", "Constitutive", "Human", "Skin", "Color.", "PLoS", "ONE", "7(7):", "e41160.", "doi:10.1371/journal.pone.0041160", "Editor:", "Andrzej", "T.", "Slominski,", "University", "of", "Tennessee,", "United", "States", "of", "America", "Received", "March", "30,", "2012;", "Accepted", "June", "18,", "2012;", "Published", "July", "23,", "2012", "Copyright:", "2012", "Yoshida-Amano", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "These", "authors", "have", "no", "support", "or", "funding", "to", "report.", "Competing", "Interests:", "The", "authors", "have", "read", "the", "journal’s", "policy", "and", "have", "the", "following", "conflicts:", "Yasuko", "Yoshida-Amano,", "Akira", "Hachiya,", "Atsushi", "Ohuchi,", "Takashi", "Kitahara,", "and", "Yoshinori", "Takema", "are", "employed", "by", "Kao", "Corporation,", "who", "were", "the", "funders", "of", "this", "study.", "There", "are", "no", "patents,", "products", "in", "development", "or", "marketed", "products", "to", "declare.", "This", "does", "not", "alter", "the", "authors’", "adherence", "to", "all", "the", "PLoS", "ONE", "policies", "on", "sharing", "data", "and", "materials.", "*", "E-mail:", "hachiya.akira@kao.co.jp", "Introduction", "Skin", "color", "is", "predominantly", "determined", "by", "the", "amount", "and", "types", "of", "melanin", "produced", "in", "melanosomes,", "melanocyte-specific", "organelles.", "In", "the", "process", "of", "mammal’s", "skin", "color", "formation,", "melanin", "synthesis", "is", "launched", "by", "the", "melanogenic", "enzymes,", "tyrosinase,", "dopachrome", "tautomerase", "and", "tyrosinase-related", "pro-", "tein-1,", "mutations", "in", "which", "cause", "hypopigmented", "or", "diluted", "color", "of", "skin", "[1,2].", "In", "addition", "to", "those", "enzymes,", "L-tyrosine", "and", "L-", "dihydroxyphenylalanine", "have", "also", "been", "shown", "to", "positively", "regulate", "melanin", "synthesis", "through", "the", "stimulation", "of", "tyrosinase", "activity", "[3].", "Pigmented", "melanosomes", "are", "then", "transported", "towards", "the", "cell", "membrane", "at", "the", "dendrite", "tips", "of", "melanocytes", "via", "the", "intracellular", "transport", "system,", "anchored", "to", "the", "plasma", "membrane,", "and", "then", "transferred", "to", "neighboring", "keratinocytes", "[4].", "After", "their", "transfer", "to", "keratinocytes,", "melanosomes", "are", "distributed", "around", "the", "nuclei", "by", "a", "microtubule-associated", "motor", "protein,", "dynein,", "to", "form", "supranuclear", "melanin", "caps", "which", "protect", "keratinocytes", "from", "the", "harmful", "effects", "of", "ultraviolet", "exposure", "[5,6].", "The", "substantial", "interaction", "between", "melanocytes", "and", "keratinocytes", "has", "been", "proposed", "by", "the", "anatomical", "finding", "that", ",36", "viable", "keratinocytes", "surround", "each", "melanocyte", "to", "form", "a", "specialized", "cell", "group", "called", "the", "epidermal", "melanin", "unit", "[7,8].", "This", "ratio", "of", "the", "two", "cell", "types", "is", "consistently", "kept", "despite", "the", "extremely", "wide", "range", "of", "human", "skin", "color.", "Melanogenesis", "is", "controlled", "by", "a", "wide", "range", "of", "molecular-based", "mechanisms", "in", "melanocytes", "and", "keratinocytes", "[8],", "which", "result", "in", "the", "variety", "of", "skin", "and", "hair", "pigmentation.", "Among", "them,", "melanocyte", "stimulating", "hormone", "(MSH)", "and", "its", "receptor,", "MC1R,", "which", "regulate", "melanogenic", "signaling", "via", "cAMPs,", "have", "been", "actively", "investigated.", "Genetic", "and", "cellular", "studies", "have", "revealed", "that", "MC1R", "polymorphisms", "contribute", "to", "the", "differences", "in", "the", "ultraviolet", "sensitivity", "and", "in", "hair", "and", "skin", "color", "intensity", "in", "several", "ethnic", "groups", "[9,10].", "Recently,", "melanocytes", "themselves", "PLoS", "ONE", "|", "www.plosone.org", "1", "July", "2012", "|", "Volume", "7", "|", "Issue", "7", "|", "e41160" ]

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[ "Hindawi", "Publishing", "Corporation", "Sarcoma", "Volume", "2012,", "Article", "ID", "291705,", "8", "pages", "doi:10.1155/2012/291705", "Review", "Article", "Sarcoma", "Stem", "Cells:", "Do", "We", "Know", "What", "We", "Are", "Looking", "for?", "Matteo", "Trucco", "and", "David", "Loeb", "Division", "of", "Pediatric", "Oncology,", "Department", "of", "Oncology,", "Sidney", "Kimmel", "Comprehensive", "Cancer", "Center,", "Johns", "Hopkins", "University,", "Bunting-Blaustein", "Cancer", "Research", "Building,", "Room", "2M51,", "1650", "Orleans", "Street,", "Baltimore,", "MD", "21231,", "USA", "Correspondence", "should", "be", "addressed", "to", "David", "Loeb,", "loebda@jhmi.edu", "Received", "7", "December", "2011;", "Revised", "20", "February", "2012;", "Accepted", "20", "February", "2012", "Academic", "Editor:", "Igor", "Matushansky", "Copyright", "©", "2012", "M.", "Trucco", "and", "D.", "Loeb.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Sarcomas", "represent", "a", "heterogeneous", "group", "of", "cancers", "thought", "to", "originate", "from", "malignant", "transformation", "of", "mesenchymal", "cells.", "There", "is", "increasing", "evidence", "that", "many,", "if", "not", "all,", "sarcomas", "contain", "within", "them", "tumor-initiating,", "or", "“cancer", "stem,”", "cells", "responsible", "for", "the", "initiation,", "maintenance,", "and", "potentially", "relapse", "and", "metastasis", "of", "the", "tumor.", "Various", "techniques", "have", "been", "adopted", "in", "recent", "years", "to", "identify", "putative", "sarcoma", "stem", "cell", "populations.", "The", "goal", "of", "this", "paper", "is", "to", "summarize", "the", "criteria", "used", "to", "identify", "a", "stem", "cell", "population,", "describe", "the", "more", "prominent", "markers", "and", "techniques", "used", "to", "isolate", "cancer", "stem", "cells", "in", "sarcomas,", "and", "review", "the", "evidence", "for", "the", "existence", "of", "cancer", "stem", "cells", "in", "sarcomas.", "1.", "Introduction", "Sarcomas", "represent", "a", "heterogeneous", "group", "of", "cancers", "that", "seem", "to", "originate", "from", "malignant", "transformation", "of", "mes-", "enchymal", "cells.", "Whether", "they", "represent", "malignant", "transfor-", "mation", "of", "mesenchymal", "stem", "cells", "or", "of", "differentiated", "cells", "of", "mesenchymal", "origin", "has", "not", "been", "established.", "There", "is", "increasing", "evidence", "that", "many,", "if", "not", "all,", "cancers", "constitute", "a", "hierarchy", "of", "cells", "including", "so-called", "cancer", "stem", "cells", "that", "are", "believed", "to", "be", "the", "progenitor", "cells", "from", "which", "the", "tumor", "was", "spawned", "and", "that", "these", "cancer", "stem", "cells", "may", "be", "responsible", "for", "relapses", "and", "metastases", "[1].", "Cancer", "stem", "cells", "appear", "to", "be", "resistant", "to", "chemotherapy,", "may", "remain", "quiescent", "for", "extended", "periods,", "perhaps", "have", "an", "affinity", "for", "hypoxic", "environments,", "and", "may", "have", "a", "predisposition", "for", "migration", "and", "metastasis.", "Additionally,", "since", "the", "cancer", "stem", "cell", "model", "suggests", "that", "these", "cells", "make", "up", "a", "very", "small", "portion", "of", "the", "tumor", "bulk,", "the", "majority", "being", "their", "progeny,", "the", "model", "also", "would", "offer", "an", "explanation", "for", "relapses", "that", "occur", "despite", "what", "would", "appear", "to", "be", "a", "total", "response", "to", "initial", "therapeutic", "interventions.", "An", "underlying", "matter", "is", "the", "origin", "of", "cancer", "stem", "cells.", "The", "use", "of", "the", "term", "“cancer", "stem", "cells”", "is", "suggestive", "that", "these", "are", "normal", "stem", "cells", "that", "have", "undergone", "malignant", "transformation", "and", "thus", "have", "become", "cancerous.", "Though", "this", "interpretation", "is", "understandable", "and", "this", "is", "a", "plausible", "source", "of", "cancer", "stem", "cells,", "it", "is", "by", "no", "means", "established", "that", "this", "is", "how", "cancer", "stem", "cells", "come", "to", "be.", "Alternatively,", "cancer", "stem", "cells", "may", "derive", "from", "differentiated", "cells", "that,", "through", "malignant", "transformation,", "acquire", "properties", "reminiscent", "of", "stem", "cells.", "To", "avoid", "the", "ambiguity", "of", "the", "term", "“cancer", "stem", "cell,”", "for", "the", "remainder", "of", "this", "review", "the", "terms", "tumor-", "initiating", "cell", "(TIC)", "and", "sarcoma-initiating", "cell", "(SIC)", "will", "be", "used.", "To", "better", "study", "SICs", "and", "develop", "therapies", "to", "target", "them,", "they", "must", "first", "be", "identified", "and", "isolated.", "Several", "techniques", "for", "identifying", "and", "isolating", "TIC", "have", "been", "used", "with", "varying", "success", "in", "other", "more", "common", "malignancies,", "and", "these", "techniques", "are", "being", "studied", "on", "the", "gamut", "of", "sarcomas.", "Most", "of", "these", "techniques", "involve", "identifying", "a", "subpopulation", "of", "cancer", "cells", "that", "have", "properties", "typically", "seen", "only", "in", "normal", "stem", "cells.", "We", "will", "describe", "the", "more", "prominent", "techniques", "for", "TIC", "identification", "and", "isolation", "being", "used", "in", "sarcomas", "(Table", "1)", "and", "discuss", "the", "evidence", "supporting", "the", "existence", "of", "SICs.", "2.", "Stem", "Cell", "Assays", "The", "definition", "of", "a", "TIC", "and", "the", "means", "by", "which", "to", "determine", "that", "a", "population", "contains", "TICs", "remain", "points", "of", "contention" ]

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[ "Curr", "Hematol", "Malig", "Rep", "(2012)", "7:133–143", "DOI", "10.1007/s11899-012-0122-5", "ACUTE", "LYMPHOCYTIC", "LEUKEMIA", "(F", "RAVANDI,", "SECTION", "EDITOR)", "Cytogenetic", "and", "Molecular", "Predictors", "of", "Outcome", "in", "Acute", "Lymphocytic", "Leukemia:", "Recent", "Developments", "Ilaria", "Iacobucci", "&", "Cristina", "Papayannidis", "&", "Annalisa", "Lonetti", "&", "Anna", "Ferrari", "&", "Michele", "Baccarani", "&", "Giovanni", "Martinelli", "Published", "online:", "20", "April", "2012", "#", "The", "Author(s)", "2012.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "During", "the", "last", "decade", "a", "tremendous", "technologic", "progress", "based", "on", "genome-wide", "profiling", "of", "genetic", "aberra-", "tions,", "structural", "DNA", "alterations,", "and", "sequence", "variations", "has", "allowed", "a", "better", "understanding", "of", "the", "molecular", "basis", "of", "pediatric", "and", "adult", "B/T-", "acute", "lymphoblastic", "leukemia", "(ALL),", "contributing", "to", "a", "better", "recognition", "of", "the", "biological", "heterogeneity", "of", "ALL", "and", "to", "a", "more", "precise", "definition", "of", "risk", "factors.", "Importantly,", "these", "advances", "identified", "novel", "potential", "targets", "for", "therapeutic", "intervention.", "This", "review", "will", "be", "focused", "on", "the", "cytogenetic/molecular", "advances", "in", "pediatric", "and", "adult", "ALL", "based", "on", "recently", "published", "articles.", "Keywords", "ALL", ".", "Acute", "lymphoblastic", "leukemia", ".", "SNP", "array", ".", "Next", "generation", "sequencing", "Introduction", "ALL", "represents", "a", "biologically", "and", "clinically", "heteroge-", "neous", "group", "of", "B/T-precursor-stage", "lymphoid", "cell", "ma-", "lignancies", "arising", "from", "genetic", "insults", "that", "block", "lymphoid", "differentiation", "and", "drive", "aberrant", "cell", "I.", "Iacobucci", "(*)", ":", "C.", "Papayannidis", ":", "A.", "Ferrari", ":", "M.", "Baccarani", ":", "G.", "Martinelli", "Department", "of", "Hematology", "and", "Oncological", "Sciences", "“L.", "and", "A.", "Seràgnoli”,", "University", "of", "Bologna,", "Via", "Massarenti,", "9,", "40138", "Bologna,", "Italy", "e-mail:", "ilaria.iacobucci2@unibo.it", "A.", "Lonetti", "Department", "of", "Human", "Anatomy,", "University", "of", "Bologna,", "Cellular", "Signalling", "Laboratory,", "Bologna,", "Italy", "proliferation", "and", "survival.", "Incidence", "and", "cure", "rates", "dif-", "fer", "among", "children", "and", "adults.", "In", "children,", "ALL", "is", "the", "commonest", "malignancy", "accounting", "for", "approximately", "25", "%", "of", "childhood", "cancer", "and", "it", "has", "5-year", "event-free", "survival", "rates", "ranging", "between", "76", "%", "and", "86", "%", "in", "patients", "receiving", "protocol-based", "therapy.", "In", "adults,", "ALL", "is", "less", "common", "and", "generally", "carries", "a", "worse", "prognosis", "with", "a", "long-term", "survival", "probability", "less", "than", "35–40", "%", "[1,", "2].", "Although", "there", "is", "remarkable", "progress", "made", "in", "the", "treatment", "of", "ALL", "in", "children", "and,", "with", "less", "efficacy,", "in", "adults,", "several", "ALL", "subtypes", "continue", "to", "have", "a", "poor", "prognosis", "and", "in", "a", "proportion", "of", "long-", "term", "surviving", "patients,", "treatment", "is", "responsible", "for", "short", "and", "long-term", "toxicities.", "Consequently,", "there", "is", "a", "need", "in", "improving", "the", "molecular", "dissection", "of", "subtypes,", "identifying", "genetic", "alterations", "that", "predict", "the", "risk", "of", "treatment", "failure,", "and", "developing", "novel", "and", "targeted", "therapies.", "Cytogenetics", "has", "long", "been", "used", "for", "diagno-", "sis,", "risk", "stratification,", "and", "therapeutic", "implications,", "how-", "ever", "experimental", "models", "[3,", "4]", "have", "established", "that", "primary", "cytogenetic", "abnormalities", "alone", "are", "insufficient", "to", "induce", "leukemia", "and", "that", "cooperative", "mutations", "are", "required.", "The", "development", "of", "microarray", "technologies", "to", "profile", "gene", "expression", "and", "structural", "genetic", "alterations", "in", "a", "genome-wide", "and", "high-resolution", "fashion", "have", "rev-", "olutionized", "our", "ability", "to", "identify", "genetic", "abnormalities", "providing", "important", "insights", "into", "the", "pathways", "deregu-", "lated", "in", "ALL", "[5].", "Moreover,", "recently", "the", "development", "of", "next-generation", "sequencing", "(NGS)", "technologies", "has", "provided", "researchers", "with", "completely", "new", "and", "effective", "tools", "for", "the", "discovery", "of", "novel", "alterations,", "depicting", "an", "exhaustive", "picture", "of", "the", "leukemia", "genome", "complexity", "(Fig.", "1).", "This", "review", "emphasizes", "the", "most", "important", "and", "newest", "findings", "obtained", "from", "genomic", "analysis", "of", "B/T-", "lineage", "ALL." ]

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[ "Hindawi", "Publishing", "Corporation", "Depression", "Research", "and", "Treatment", "Volume", "2012,", "Article", "ID", "124370,", "6", "pages", "doi:10.1155/2012/124370", "Review", "Article", "Spiritually", "Integrated", "Treatment", "of", "Depression:", "A", "Conceptual", "Framework", "John", "R.", "Peteet", "Department", "of", "Psychosocial", "Oncology", "and", "Palliative", "Care,", "Dana-Farber", "Cancer", "Institute", "and", "Brigham", "and", "Women’s", "Hospital,", "Boston,", "MA", "02115,", "USA", "Correspondence", "should", "be", "addressed", "to", "John", "R.", "Peteet,", "jpeteet@partners.org", "Received", "21", "January", "2012;", "Accepted", "4", "March", "2012", "Academic", "Editor:", "Harold", "G.", "Koenig", "Copyright", "©", "2012", "John", "R.", "Peteet.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Many", "studies", "have", "found", "an", "inverse", "correlation", "between", "religious/spiritual", "involvement", "and", "depression.", "Yet", "several", "obstacles", "impede", "spiritually", "integrated", "treatment", "of", "depressed", "individuals.", "These", "include", "specialization", "and", "fragmentation", "of", "care,", "inexperience", "of", "clinicians", "and", "spiritual", "care", "providers,", "ideological", "bias,", "boundary", "and", "ethical", "concerns,", "and", "the", "lack", "of", "an", "accepted", "conceptual", "framework", "for", "integrated", "treatment.", "Here", "I", "suggest", "a", "framework", "for", "approaching", "these", "obstacles,", "constructed", "from", "a", "unified", "view", "of", "human", "experience", "(having", "emotional,", "existential,", "and", "spiritual", "dimensions);", "spirituality", "seen", "as", "a", "response", "to", "existential", "concerns", "(in", "domains", "such", "as", "identity,", "hope,", "meaning/purpose,", "morality,", "and", "autonomy", "in", "relation", "to", "authority,", "which", "are", "frequently", "distorted", "and", "amplified", "in", "depression);", "a", "rationale", "for", "locating", "spiritually", "oriented", "approaches", "within", "a", "clinician’s", "assessment,", "formulation,", "and", "treatment", "plan;", "and", "recognition", "of", "the", "challenges", "and", "potential", "pitfalls", "of", "integrated", "treatment.", "1.", "Introduction", "Depressed", "individuals", "often", "feel", "not", "only", "unfortunate", "but", "also", "that", "the", "world", "is", "oppressive,", "life", "is", "meaningless,", "and/or", "God", "is", "disapproving.", "They", "may", "question:", "“Am", "I", "clinically", "depressed,", "Or", "lacking", "in", "faith?”", "“Is", "life", "as", "unfair", "and", "empty", "as", "it", "seems?”", "“Is", "God", "punishing", "me?”", "or", "“Should", "I", "take", "an", "antidepressant,", "or", "pray", "more?”", "Because", "depression", "can", "so", "closely", "resemble", "ordinary", "spiritual", "experience,", "some", "sufferers", "resist", "treatment", "because", "they", "feel", "they", "should", "have", "more", "faith.", "Religious", "traditions", "and", "the", "communities", "that", "interpret", "them", "at", "times", "regard", "depression", "as", "an", "illness,", "at", "times", "as", "evidence", "of", "spiritual", "weakness,", "and", "at", "times", "even", "as", "a", "punishment.", "For", "their", "part,", "mental", "health", "professionals", "may", "hesitate", "to", "address", "the", "spiritual", "dimension", "of", "their", "patients’", "experience.", "Some", "view", "spirituality", "as", "an", "epiphenomenon", "of", "more", "basic", "neurobiological", "or", "evolutionary", "processes", "and", "as", "such", "of", "only", "peripheral", "interest", "to", "psychiatry.", "Others", "regard", "religion", "as", "a", "potentially", "harmful,", "immature", "form", "of", "wish", "fulfillment.", "Still", "others", "have", "ethical", "concerns", "about", "charging", "patients", "and/or", "their", "insurance", "companies", "for", "spiritually", "oriented", "interventions", "or", "about", "influencing", "patients", "on", "the", "basis", "of", "their", "own", "personal", "values.", "Many", "lack", "sufficient", "familiarity", "with", "their", "patients’", "spiritual", "traditions", "and/or", "experience", "to", "collaborate", "effectively", "with", "religious", "professionals", "and/or", "retain", "unresolved", "conflicts", "in", "their", "own", "relationship", "with", "spiritual", "authorities.", "A", "growing", "literature", "describes", "the", "spiritual", "dimension", "of", "depression", "as", "experienced", "by", "its", "sufferers", "[1–3],", "epidemio-", "logic", "and", "other", "evidence", "for", "religion", "as", "a", "risk", "and", "protective", "factor", "[4–6],", "the", "social", "dimension", "of", "depression", "[7,", "8],", "the", "potential", "for", "spiritual", "growth", "in", "the", "face", "of", "adversity", "[9],", "ways", "for", "depressed", "individuals", "to", "draw", "upon", "the", "resources", "of", "a", "particular", "faith", "tradition", "[10],", "frameworks", "for", "addressing", "spiritual", "issues", "generally", "in", "psychotherapy", "[11–15],", "and", "evidence", "for", "the", "effectiveness", "of", "spiritual", "interventions", "in", "depression", "[16–18].", "However,", "the", "literature", "has", "lacked", "a", "practical,", "comprehensive", "way", "of", "approaching", "the", "spiritually", "integrated", "treatment", "of", "depressed", "individuals", "of", "any", "spiritual", "tradition", "or", "of", "none.", "What", "follows", "is", "a", "conceptual", "framework", "for", "approaching", "the", "complex", "relationship", "among", "depression,", "spirituality,", "and", "mental", "health", "treatment,", "which", "I", "more", "fully", "describe", "in", "Depression", "and", "the", "Soul:", "A", "Guide", "to", "Spiritually", "Integrated", "Treatment", "[19]." ]

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[ "Brief", "Definitive", "Report", "Activated", "Akt", "Protects", "the", "Lung", "from", "Oxidant-induced", "Injury", "and", "Delays", "Death", "of", "Mice", "By", "Yunbiao", "Lu,*", "Lisa", "Parkyn,*", "Leo", "E.", "Otterbein,*", "Yasuko", "Kureishi,‡", "Kenneth", "Walsh,‡", "Anuradha", "Ray,*", "and", "Prabir", "Ray*", "From", "the", "*Department", "of", "Internal", "Medicine,", "Pulmonary", "and", "Critical", "Care", "Section,Yale", "University", "School", "of", "Medicine,", "New", "Haven,", "Connecticut", "06520;", "the", "‡Division", "of", "Cardiovascular", "Research,", "St.", "Elizabeth’s", "Medical", "Center", "and", "Program", "in", "Cell,", "Molecular", "and", "Developmental", "Biology,", "Sackler", "School", "of", "Biomedical", "Studies,Tufts", "University", "School", "of", "Medicine,", "Boston,", "Massachusetts", "02135", "Abstract", "Oxidant-induced", "injury", "to", "the", "lung", "causes", "extensive", "damage", "to", "lung", "epithelial", "cells.", "Impaired", "protection", "and", "repair", "of", "the", "lung", "epithelium", "can", "result", "in", "death.", "The", "serine-threonine", "kinase", "Akt", "has", "been", "implicated", "in", "inhibiting", "cell", "death", "induced", "by", "different", "stimuli", "including", "growth", "factor", "withdrawal,", "cell", "cycle", "discordance,", "DNA", "damage,", "and", "loss", "of", "cell", "adhesion", "in", "different", "cell", "types.", "However,", "the", "in", "vivo", "relevance", "of", "this", "prosurvival", "pathway", "has", "not", "been", "explored.", "Here", "we", "show", "that", "a", "constitutively", "active", "form", "of", "Akt", "introduced", "intratracheally", "into", "the", "lungs", "of", "mice", "by", "adenovirus", "gene", "transfer", "techniques", "protects", "mice", "from", "hyperoxic", "pulmonary", "dam-", "age", "and", "delays", "death", "of", "mice.", "This", "is", "the", "first", "demonstration", "of", "the", "in", "vivo", "protective", "function", "of", "Akt", "in", "the", "context", "of", "oxidant-induced", "lung", "injury.", "Key", "words:", "hyperoxia", "•", "lung", "•", "Akt", "•", "apoptosis", "•", "survival", "Introduction", "Oxygen", "therapy", "is", "administered", "to", "decrease", "tissue", "hypoxia", "and", "to", "relieve", "arterial", "hypoxemia", "in", "patients", "with", "acute", "and", "chronic", "cardiovascular", "and", "pulmonary", "diseases", "and", "also", "to", "premature", "babies", "with", "respiratory", "distress", "syndrome.", "How-", "ever,", "hyperoxia", "can", "cause", "acute", "lung", "injury", "which", "results", "in", "increased", "lung", "water", "with", "protein-rich", "edema", "fluid", "spilling", "into", "the", "interstitial", "and", "alveolar", "spaces.", "This", "is", "thought", "to", "occur", "after", "injury", "to", "epithelial", "and", "capillary", "endothelial", "cells", "resulting", "in", "epithelial", "cell", "death", "and", "increased", "pulmonary", "capillary", "permeability", "(1,", "2).", "Current", "evidence", "indicates", "that", "the", "damaging", "effects", "of", "oxygen", "are", "caused", "by", "reactive", "oxygen", "intermediates", "(ROIs)", "such", "as", "the", "superoxide", "anion", "(O22)", "that", "are", "formed", "in", "the", "presence", "of", "excessive", "oxygen.", "Severe", "oxidant-induced", "stress", "can", "result", "in", "respiratory", "fail-", "ure", "and", "even", "death", "(3).", "Akt/PKB", "is", "homologous", "to", "the", "protein", "kinases", "PKA", "and", "PKC", "(and", "hence", "the", "name", "PKB", "or", "related", "to", "A", "and", "C", "pro-", "tein", "kinase", "[RAC-PK];", "reference", "4).", "Akt", "is", "activated", "by", "phosphatidylinositol", "(PI)", "3-kinase", "in", "response", "to", "growth", "and", "survival", "factors", "(5).", "It", "has", "been", "shown", "that", "after", "stimula-", "tion", "by", "growth", "factors,", "Akt", "undergoes", "phosphorylation", "at", "Address", "correspondence", "to", "P.", "Ray,", "Department", "of", "Internal", "Medicine,", "Pulmonary", "and", "Critical", "Care", "Section,", "Yale", "University", "School", "of", "Medicine,", "333", "Cedar", "St.,", "LCI", "105,", "New", "Haven,", "CT", "06520.", "Phone:", "203-", "785-3620;", "Fax:", "203-785-3826;", "E-mail:", "prabir.ray@yale.edu", "residues", "Thr308", "in", "the", "activation", "loop", "of", "the", "kinase", "and", "at", "Ser473", "in", "the", "carboxy", "terminus", "(6,", "7).", "A", "downstream", "path-", "way", "that", "is", "induced", "by", "activation", "of", "the", "PI", "3-kinase/Akt", "pathway", "is", "the", "phosphorylation", "of", "the", "Bcl-2", "family", "member", "Bad,", "which", "releases", "Bcl-XL", "thereby", "promoting", "cell", "survival", "(8,", "9).", "A", "second", "downstream", "prosurvival", "mechanism", "in-", "volves", "the", "transcription", "factor", "forkhead,", "the", "phosphoryla-", "tion", "of", "which", "by", "Akt", "prevents", "its", "nuclear", "translocation", "and", "activation", "of", "genes", "that", "promote", "apoptosis", "(10).", "Several", "studies", "indicate", "that", "Akt", "activation", "plays", "an", "important", "role", "in", "inhibiting", "cell", "apoptosis", "in", "fibroblasts,", "epithelial", "and", "lym-", "phoid", "cell", "lines,", "and", "neuronal", "cells", "(11–16).", "However,", "these", "studies", "with", "Akt", "have", "been", "carried", "out", "in", "vitro", "and", "the", "in", "vivo", "significance", "of", "this", "pathway", "in", "protection", "from", "cell", "death", "induced", "by", "different", "stimuli", "including", "oxidative", "stress", "remains", "to", "be", "investigated.", "Here", "we", "demonstrate", "that", "ex-", "pression", "of", "a", "constitutively", "active", "derivative", "of", "Akt", "in", "the", "mouse", "lung", "by", "adenovirus", "gene", "transfer", "methods", "protects", "lungs", "and", "delays", "death", "from", "oxidant-induced", "injury.", "Materials", "and", "Methods", "Cells", "and", "Adenovirus", "Constructs.", "Human", "primary", "small", "air-", "way", "epithelial", "(SAE)", "cells", "were", "obtained", "from", "Clonetics", "and", "grown", "in", "supplied", "medium.", "The", "virus", "packaging", "cell", "line", "293", "was", "grown", "in", "DMEM", "supplemented", "with", "10%", "FBS.", "The", "gener-", "545", "J.", "Exp.", "Med.", "The", "Rockefeller", "University", "Press", "•", "0022-1007/2001/02/545/05", "$5.00", "Volume", "193,", "Number", "4,", "February", "19,", "2001", "545–549", "http://www.jem.org/cgi/content/full/193/4/545" ]

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[ "PLoS", "MEDICINE", "Live,", "Attenuated", "Influenza", "A", "H5N1", "Candidate", "Vaccines", "Provide", "Broad", "Cross-Protection", "in", "Mice", "and", "Ferrets", "1[", "Amorsolo", "L.", "Suguitan", "Jr.", ",", "Josephine", "McAuliffe1[,", "Kimberly", "L.", "Mills1,", "Hong", "Jin2,", "Greg", "Duke2,", "Bin", "Lu2,", "Catherine", "J.", "Luke", "1", ",", "Brian", "Murphy", "1", ",", "David", "E.", "Swayne", "3", ",", "George", "Kemble2,", "Kanta", "Subbarao1*", "1", "Laboratory", "of", "Infectious", "Diseases,", "National", "Institute", "of", "Allergy", "and", "Infectious", "Diseases,", "National", "Institutes", "of", "Health,", "Bethesda,", "Maryland,", "United", "States", "of", "America,", "2", "MedImmune", "Vaccines,", "Mountain", "View,", "California,", "United", "States", "of", "America,", "3", "Southeast", "Poultry", "Research", "Laboratory,", "Agricultural", "Research", "Service,", "United", "States", "Department", "of", "Agriculture,", "Athens,", "Georgia,", "United", "States", "of", "America", "Funding:", "This", "research", "was", "supported", "in", "part", "by", "the", "Intramural", "Research", "Program", "of", "the", "NIH,", "NIAID.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "Academic", "Editor:", "Joseph", "S.", "M.", "Peiris,", "The", "University", "of", "Hong", "Kong,", "China", "Citation:", "Suguitan", "AL", "Jr.,", "McAuliffe", "J,", "Mills", "KL,", "Jin", "H,", "Duke", "G,", "et", "al.", "(2006)", "Live,", "attenuated", "influenza", "A", "H5N1", "candidate", "vaccines", "provide", "broad", "cross-protection", "in", "mice", "and", "ferrets.", "PLoS", "Med", "3(9):", "e360.", "DOI:", "10.1371/", "journal.pmed.0030360", "Received:", "April", "25,", "2006", "Accepted:", "August", "1,", "2006", "Published:", "September", "12,", "2006", "DOI:", "10.1371/journal.pmed.0030360", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Public", "Domain", "declaration", "which", "stipulates", "that,", "once", "placed", "in", "the", "public", "domain,", "this", "work", "may", "be", "freely", "reproduced,", "distributed,", "transmitted,", "modified,", "built", "upon,", "or", "otherwise", "used", "by", "anyone", "for", "any", "lawful", "purpose.", "Abbreviations:", "AA,", "influenza", "A/Ann", "Arbor/6/60;", "att,", "attenuation;", "BSL,", "biosafety", "level;", "ca,", "cold-adapted;", "CEF,", "chick", "embryo", "fibroblast;", "CPE,", "cytopathic", "effect;", "EID50,", "50%", "egg", "infectious", "dose;", "HA,", "hemagglutinin;", "HAI,", "hemagglutination", "inhibition;", "HPAI,", "highly", "pathogenic", "avian", "influenza;", "LD50,", "50%", "lethal", "dose;", "MDCK,", "Madin-Darby", "canine", "kidney;", "NA,", "neuraminidase;", "p.i.,", "postinfection;", "pfu,", "plaque-forming", "unit(s);", "SE,", "standard", "error;", "SPF,", "specific", "pathogen-free;", "TCID50,", "50%", "tissue", "culture", "infectious", "dose;", "ts,", "temperature", "sensitive;", "wt,", "wild-type", "*", "To", "whom", "correspondence", "should", "be", "addressed.", "E-mail:", "ksubbarao@", "niaid.nih.gov", "[", "These", "authors", "contributed", "equally", "to", "this", "work.", "A", "B", "S", "T", "R", "A", "C", "T", "Background", "Recent", "outbreaks", "of", "highly", "pathogenic", "influenza", "A", "H5N1", "viruses", "in", "humans", "and", "avian", "species", "that", "began", "in", "Asia", "and", "have", "spread", "to", "other", "continents", "underscore", "an", "urgent", "need", "to", "develop", "vaccines", "that", "would", "protect", "the", "human", "population", "in", "the", "event", "of", "a", "pandemic.", "Methods", "and", "Findings", "Live,", "attenuated", "candidate", "vaccines", "possessing", "genes", "encoding", "a", "modified", "H5", "hemag-", "glutinin", "(HA)", "and", "a", "wild-type", "(wt)", "N1", "neuraminidase", "from", "influenza", "A", "H5N1", "viruses", "isolated", "in", "Hong", "Kong", "and", "Vietnam", "in", "1997,", "2003,", "and", "2004,", "and", "remaining", "gene", "segments", "derived", "from", "the", "cold-adapted", "(ca)", "influenza", "A", "vaccine", "donor", "strain,", "influenza", "A/Ann", "Arbor/6/60", "ca", "(H2N2),", "were", "generated", "by", "reverse", "genetics.", "The", "H5N1", "ca", "vaccine", "viruses", "required", "trypsin", "for", "efficient", "growth", "in", "vitro,", "as", "predicted", "by", "the", "modification", "engineered", "in", "the", "gene", "encoding", "the", "HA,", "and", "possessed", "the", "temperature-sensitive", "and", "attenuation", "phenotypes", "specified", "by", "the", "internal", "protein", "genes", "of", "the", "ca", "vaccine", "donor", "strain.", "More", "importantly,", "the", "candidate", "vaccines", "were", "immunogenic", "in", "mice.", "Four", "weeks", "after", "receiving", "a", "single", "dose", "of", "106", "50%", "tissue", "culture", "infectious", "doses", "of", "intranasally", "administered", "vaccines,", "mice", "were", "fully", "protected", "from", "lethality", "following", "challenge", "with", "homologous", "and", "antigenically", "distinct", "heterologous", "wt", "H5N1", "viruses", "from", "different", "genetic", "sublineages", "(clades", "1,", "2,", "and", "3)", "that", "were", "isolated", "in", "Asia", "between", "1997", "and", "2005.", "Four", "weeks", "after", "receiving", "two", "doses", "of", "the", "vaccines,", "mice", "and", "ferrets", "were", "fully", "protected", "against", "pulmonary", "replication", "of", "homologous", "and", "heterologous", "wt", "H5N1", "viruses.", "Conclusions", "The", "promising", "findings", "in", "these", "preclinical", "studies", "of", "safety,", "immunogenicity,", "and", "efficacy", "of", "the", "H5N1", "ca", "vaccines", "against", "antigenically", "diverse", "H5N1", "vaccines", "provide", "support", "for", "their", "careful", "evaluation", "in", "Phase", "1", "clinical", "trials", "in", "humans.", "The", "Editors’", "Summary", "of", "this", "article", "follows", "the", "references.", "PLoS", "Medicine", "|", "www.plosmedicine.org", "1541", "September", "2006", "|", "Volume", "3", "|", "Issue", "9", "|", "e360" ]

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[ "Handel", "and", "Ramagopalan", "BMC", "Medical", "Genetics", "2010,", "11:73", "http://www.biomedcentral.com/1471-2350/11/73", "D", "E", "B", "A", "T", "E", "Open", "Access", "IDsebLataemarckian", "evolution", "relevant", "to", "medicine?", "Adam", "E", "Handel1,2", "and", "Sreeram", "V", "Ramagopalan*1,2", "Abstract", "Background:", "200", "years", "have", "now", "passed", "since", "Darwin", "was", "born", "and", "scientists", "around", "the", "world", "are", "celebrating", "this", "important", "anniversary", "of", "the", "birth", "of", "an", "evolutionary", "visionary.", "However,", "the", "theories", "of", "his", "colleague", "Lamarck", "are", "treated", "with", "considerably", "less", "acclaim.", "These", "theories", "centre", "on", "the", "tendency", "for", "complexity", "to", "increase", "in", "organisms", "over", "time", "and", "the", "direct", "transmission", "of", "phenotypic", "traits", "from", "parents", "to", "offspring.", "Discussion:", "Lamarckian", "concepts,", "long", "thought", "of", "no", "relevance", "to", "modern", "evolutionary", "theory,", "are", "enjoying", "a", "quiet", "resurgence", "with", "the", "increasing", "complexity", "of", "epigenetic", "theories", "of", "inheritance.", "There", "is", "evidence", "that", "epigenetic", "alterations,", "including", "DNA", "methylation", "and", "histone", "modifications,", "are", "transmitted", "transgenerationally,", "thus", "providing", "a", "potential", "mechanism", "for", "environmental", "influences", "to", "be", "passed", "from", "parents", "to", "offspring:", "Lamarckian", "evolution.", "Furthermore,", "evidence", "is", "accumulating", "that", "epigenetics", "plays", "an", "important", "role", "in", "many", "common", "medical", "conditions.", "Summary:", "Epigenetics", "allows", "the", "peaceful", "co-existence", "of", "Darwinian", "and", "Lamarckian", "evolution.", "Further", "efforts", "should", "be", "exerted", "on", "studying", "the", "mechanisms", "by", "which", "this", "occurs", "so", "that", "public", "health", "measures", "can", "be", "undertaken", "to", "reverse", "or", "prevent", "epigenetic", "changes", "important", "in", "disease", "susceptibility.", "Perhaps", "in", "2059", "we", "will", "be", "celebrating", "the", "anniversary", "of", "both", "Darwin", "and", "Lamarck.", "Background", "The", "200th", "anniversary", "of", "the", "birth", "of", "Charles", "Robert", "Dar-", "win", "FRS", "is", "rightly", "being", "celebrated", "across", "the", "world", "in", "2009", "[1,2].", "Another", "event", "of", "interest", "in", "1809,", "now", "largely", "forgotten,", "was", "the", "publication", "of", "Jean-Baptiste", "Pierre", "Antoine", "de", "Monet,", "Chevalier", "de", "la", "Marck's", "(Lamarck)", "philosophie", "zoologique", "ou", "exposition", "des", "considérations", "relatives", "à", "l'histoire", "naturelle", "des", "animaux", "[3].", "Despite", "this", "work", "being", "the", "first", "formally", "published", "evolutionary", "theory,", "it", "garners", "little", "praise", "today.", "This", "was", "largely", "due", "to", "the", "widespread", "derision", "it", "received,", "most", "notably", "from", "Lamarck's", "colleague,", "Georges", "Cuvier", "[4].", "Do", "Lamarck's", "ideas", "deserve", "to", "be", "forgotten?", "As", "nearly", "all", "current", "litera-", "ture", "paints", "a", "disparaging", "view", "of", "Lamarck", "by", "referring", "to", "his", "supposition", "as", "to", "how", "giraffes", "acquired", "their", "charac-", "teristic", "morphology,", "it", "seems", "worthwhile", "to", "go", "back", "to", "review", "Lamarck's", "original", "texts.", "In", "this", "way", "we", "can", "assess", "the", "relevance", "of", "his", "thought", "on", "evolution", "to", "our", "current,", "ever", "expanding,", "knowledge", "of", "heredity", "though", "eyes", "unbi-", "ased", "by", "the", "modern,", "depreciatory", "view", "of", "his", "work.", "*", "Correspondence:", "sreeramr@well.ox.ac.uk", "1", "Wellcome", "Trust", "Centre", "for", "Human", "Genetics,", "University", "of", "Oxford,", "Roosevelt", "Drive,", "Headington,", "Oxford,", "OX3", "7BN,", "UK", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "Philosophie", "zoologique", "was", "studied", "by", "Stephen", "Jay", "Gould", "[4]", "among", "others.", "Lamarck's", "evolutionary", "theory", "can", "essentially", "be", "summarised", "with", "two", "concepts.", "The", "first", "is", "that", "organisms", "gradually", "and", "progressively", "become", "more", "complex", "by", "a", "\"prime", "cause\"", "and", "the", "second", "is", "that", "this", "progression", "is", "influenced", "by", "external", "condi-", "tions:", "\"the", "environment", "exercises", "a", "great", "influence", "over", "the", "activities", "of", "animals,", "and", "as", "a", "result", "of", "this", "influence", "the", "increased", "and", "sustained", "use", "or", "disuse", "of", "any", "organ", "are", "causes", "of", "modification", "of", "the", "organization", "and", "shape", "of", "animals\"", "[3,4].", "This", "second", "concept", "leads", "to", "Lamarck's", "well", "known", "idea", "of", "acquired", "or", "soft", "inheritance:", "\"the", "law", "of", "nature", "by", "which", "new", "individuals", "receive", "all", "that", "has", "been", "acquired", "in", "organization", "during", "the", "lifetime", "of", "their", "parents", "is", "so", "true,", "so", "striking....\"", "[3,4].", "Discussion", "After", "two", "centuries", "is", "there", "any", "evidence", "to", "support", "Lamarck's", "concepts?", "A", "number", "of", "studies", "do", "actually", "point", "to", "the", "existence", "of", "acquired", "characteristics", "and", "sometimes", "their", "inheritance.", "In", "rats,", "for", "example,", "stressed", "mothers", "have", "less", "time", "to", "care", "for", "offspring", "through", "postnatal", "licking/grooming", "(LG)", "and", "arched-", "back", "nursing", "(ABN)", "[5].", "Low", "levels", "of", "postnatal", "LG", "and", "ABN", "result", "in", "offspring", "being", "more", "apprehensive,", "in", "©", "2010", "Handel", "and", "Ramagopalan;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Cre-", "BioMed", "Central", "ative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "re-", "production", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CTLA-4–Ig", "Activates", "Forkhead", "Transcription", "Factors", "and", "Protects", "Dendritic", "Cells", "from", "Oxidative", "Stress", "in", "Nonobese", "Diabetic", "Mice", "Francesca", "Fallarino,1", "Roberta", "Bianchi,1", "Ciriana", "Orabona,1", "Carmine", "Vacca,1", "Maria", "L.", "Belladonna,1", "Maria", "C.", "Fioretti,1", "David", "V.", "Serreze,2", "Ursula", "Grohmann,1", "and", "Paolo", "Puccetti1", "1Department", "of", "Experimental", "Medicine,", "University", "of", "Perugia,", "Perugia", "06126,", "Italy", "2The", "Jackson", "Laboratory,", "Bar", "Harbor,", "ME", "04609", "Abstract", "Prediabetes", "and", "diabetes", "in", "nonobese", "diabetic", "(NOD)", "mice", "have", "been", "targeted", "by", "a", "variety", "of", "immunotherapies,", "including", "the", "use", "of", "a", "soluble", "form", "of", "cytotoxic", "T", "lymphocyte", "antigen", "4", "(CTLA-4)", "and", "interferon", "(IFN)-", ".", "The", "cytokine,", "however,", "fails", "to", "activate", "tolerogenic", "properties", "in", "dendritic", "cells", "(DCs)", "from", "highly", "susceptible", "female", "mice", "early", "in", "prediabetes.", "The", "defect", "is", "characterized", "by", "impaired", "induction", "of", "immunosuppressive", "tryptophan", "catabolism,", "is", "related", "to", "transient", "blockade", "of", "the", "signal", "transducer", "and", "activator", "of", "transcription", "(STAT)1", "pathway", "of", "intracellular", "signaling", "by", "IFN-", ",", "and", "is", "caused", "by", "peroxynitrite", "production.", "Here,", "we", "show", "that", "soluble", "CTLA-4", "imparts", "suppressive", "properties", "to", "DCs", "from", "early", "prediabetic", "NOD", "female", "mice", "through", "mechanisms", "that", "rely", "on", "autocrine", "signaling", "by", "IFN-", ".", "Although", "phosphorylation", "of", "STAT1", "in", "response", "to", "IFN-", "is", "compromised", "in", "those", "mice,", "CTLA-4", "obviates", "the", "defect.", "IFN-", "–driven", "expression", "of", "tryptophan", "catabolism", "by", "CTLA-4–immunoglobulin", "is", "made", "possible", "through", "the", "concomitant", "activation", "of", "the", "Forkhead", "Box", "class", "O", "(FOXO)", "transcription", "factor", "FOXO3a,", "induction", "of", "the", "superoxide", "dismutase", "gene,", "and", "prevention", "of", "peroxynitrite", "formation.", "Key", "words:", "NOD", "mice", "•", "dendritic", "cells", "•", "CTLA-4", "•", "superoxide", "dismutase", "•", "signal", "transduction", "Introduction", "The", "nonobese", "diabetic", "(NOD)", "strain", "of", "mice", "has", "become", "a", "prototypic", "model", "of", "autoimmune", "disease", "(1).", "Most", "female", "mice", "die", "of", "type", "1", "diabetes,", "reflecting", "the", "onset", "of", "insulitis", "at", "4", "wk", "of", "age", "and", "the", "T", "cell–mediated", "destruction", "of", "pancreatic", "cells.", "Several", "defects", "have", "been", "described", "in", "NOD", "mice,", "including", "impaired", "expression", "of", "cytotoxic", "T", "lymphocyte", "antigen", "4", "(CTLA-4;", "reference", "2),", "aberrant", "APC", "function", "(3),", "and", "peroxynitrite", "formation", "(4).", "Predia-", "betes", "and", "diabetes", "have", "been", "treated", "with", "age-related", "out-", "comes", "by", "numerous,", "apparently", "disparate", "approaches,", "in-", "cluding", "administration", "of", "soluble", "CTLA-4", "(CTLA-4–Ig;", "reference", "5)", "and", "the", "use", "of", "IFN-", "(6,", "7).", "We", "have", "recently", "proposed", "a", "model", "of", "tolerance", "induction", "that", "might", "trace", "the", "activity", "of", "the", "synthetic", "immunomodula-", "tor", "CTLA-4–Ig", "(8),", "CTLA-4–expressing", "regulatory", "T", "cells", "U.", "Grohmann", "and", "P.", "Puccetti", "are", "senior", "authors", "on", "this", "paper.", "Address", "correspondence", "to", "Ursula", "Grohmann,", "Dept.", "of", "Experimental", "Medicine,", "Section", "of", "Pharmacology,", "University", "of", "Perugia,", "Via", "del", "Gio-", "chetto,", "Perugia", "06126,", "Italy.", "Phone:", "39-075-585-7460;", "Fax:", "39-075-585-", "7473;", "email:", "ugrohmann@tin.it", "(9),", "and", "recombinant", "IFN-", "(10)", "to", "a", "unitary", "mechanism.", "In", "this", "model,", "CTLA-4–Ig", "acts", "through", "B7-mediated", "signaling", "in", "tolerogenic", "DCs", "to", "promote", "release", "of", "IFN-", ",", "whose", "au-", "tocrine", "effects", "result", "in", "activation", "of", "the", "immunosuppressive", "pathway", "of", "tryptophan", "catabolism", "(11).", "However,", "IFN-", "is", "unable", "to", "induce", "tolerizing", "properties", "in", "DCs", "from", "NOD", "female", "mice", "at", "4", "wk", "of", "age,", "and", "this", "is", "apparently", "due", "to", "per-", "oxynitrite", "nitration", "of", "STAT1", "and", "blockade", "of", "IFN-", "signal-", "ing", "(12).", "The", "enzyme", "indoleamine", "2,3-dioxygenase", "(IDO)", "is", "in", "fact", "responsible", "for", "tryptophan", "degradation", "by", "DCs", "(11),", "and", "IDO", "induction", "by", "IFN-", "requires", "STAT1", "signaling", "(8).", "Transcription", "factors", "of", "the", "Forkhead", "Box", "class", "O", "(FOXO)", "family", "are", "known", "to", "act", "as", "signal", "transducers", "at", "the", "conflu-", "Abbreviations", "used", "in", "this", "paper:", "1-MT,", "1-methyl-dl-tryptophan;", "2-MeOE2,", "2-methoxyestradiol;", "CTLA-4,", "cytotoxic", "T", "lymphocyte", "antigen", "4;", "FOXO,", "Forkhead", "Box", "class", "O;", "GED,", "guanidinoethyl", "disulphide;", "IDO,", "indole-", "amine", "2,3-dioxygenase;", "MnTBAP,", "Mn(III)tetrakis(4-benzoic", "acid)porphy-", "rin", "chloride;", "NO,", "nitric", "oxide;", "NOD,", "nonobese", "diabetic;", "PI3K,", "phos-", "phatidylinositol", "3", "kinase;", "RLU,", "relative", "light", "unit;", "siRNA,", "small", "interfering", "RNA;", "SOD,", "superoxide", "dismutase.", "1051", "J.", "Exp.", "Med.", "©", "The", "Rockefeller", "University", "Press", "•", "0022-1007/2004/10/1051/12", "$8.00", "Volume", "200,", "Number", "8,", "October", "18,", "2004", "1051–1062", "http://www.jem.org/cgi/doi/10.1084/jem.20040942" ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "The", "Loss", "of", "PTEN", "Allows", "TCR", "Lineage", "Thymocytes", "to", "Bypass", "IL-7", "and", "Pre-TCR–mediated", "Signaling", "Thijs", "J.", "Hagenbeek,1,4", "Marianne", "Naspetti,1", "Fabrice", "Malergue,2", "Fabien", "Garçon,5", "Jacques", "A.", "Nunès,5", "Kitty", "B.J.M.", "Cleutjens,6", "Jan", "Trapman,6", "Paul", "Krimpenfort,3", "and", "Hergen", "Spits1,4", "1Department", "of", "Immunology,", "2Department", "of", "Cell", "Biology,", "and", "3Department", "of", "Molecular", "Genetics,", "Netherlands", "Cancer", "Institute,", "1066", "CX", "Amsterdam,", "Netherlands", "4Department", "of", "Cell", "Biology", "and", "Histology,", "University", "of", "Amsterdam,", "Academic", "Medical", "Center,", "1105", "AZ", "Amsterdam,", "Netherlands", "5Institut", "National", "de", "la", "Sante", "et", "de", "la", "Recherche", "Medicale", "UMR", "599,", "Institut", "de", "Recherches", "sur", "le", "Cancer", "de", "Marseille,", "13009", "Marseille,", "France", "6Department", "of", "Pathology,", "Erasmus", "Medical", "Centre,", "3000", "DR", "Rotterdam,", "Netherlands", "Abstract", "The", "phosphatase", "and", "tensin", "homologue", "deleted", "on", "chromosome", "10", "(PTEN)", "negatively", "regulates", "cell", "survival", "and", "proliferation", "mediated", "by", "phosphoinositol", "3", "kinases.", "We", "have", "explored", "the", "role", "of", "the", "phosphoinositol(3,4,5)P3-phosphatase", "PTEN", "in", "T", "cell", "development", "by", "analyzing", "mice", "with", "a", "T", "cell–specific", "deletion", "of", "PTEN.", "Ptenflox/floxLck-Cre", "mice", "developed", "thymic", "lym-", "phomas,", "but", "before", "the", "onset", "of", "tumors,", "they", "showed", "normal", "thymic", "cellularity.", "To", "reveal", "a", "regulatory", "role", "of", "PTEN", "in", "proliferation", "of", "developing", "T", "cells", "we", "have", "crossed", "PTEN-deficient", "mice", "with", "mice", "deficient", "for", "interleukin", "(IL)-7", "receptor", "and", "pre–T", "cell", "receptor", "(TCR)", "signaling.", "Analysis", "of", "mice", "deficient", "for", "Pten", "and", "CD3", ";", "Pten", "and", "c;", "or", "Pten,", "c,", "and", "Rag2", "revealed", "that", "deletion", "of", "PTEN", "can", "substitute", "for", "both", "IL-7", "and", "pre-TCR", "signals.", "These", "double-", "and", "triple-", "deficient", "mice", "all", "develop", "normal", "levels", "of", "CD4CD8", "double", "negative", "and", "double", "positive", "thy-", "mocytes.", "These", "data", "indicate", "that", "PTEN", "is", "an", "important", "regulator", "of", "proliferation", "of", "developing", "T", "cells", "in", "the", "thymus.", "Key", "words:", "PI-3K", "•", "thymus", "•", "Cre-LoxP", "•", "IL-7", "receptor", "•", "pre–T", "cell", "receptor", "Introduction", "T", "cell", "development", "proceeds", "through", "various", "well-defined", "transitional", "cellular", "stages.", "T", "cell", "progenitors", "are", "negative", "for", "CD4,", "CD8,", "and", "CD3", "and", "can", "be", "subdivided", "in", "four", "subpopulations", "on", "the", "basis", "of", "CD44", "(Pgp-1)", "and", "CD25", "(IL-2", "receptor", "-chain)", "surface", "expression", "(1).", "The", "most", "primitive", "of", "these", "CD4", "CD8", "(double", "negative", "[DN])", "ex-", "press", "CD44", "and", "are", "negative", "for", "CD25", "(DN1).", "These", "cells", "differentiate", "further", "into", "the", "intermediate", "DN", "stages", "with", "the", "phenotypes", "CD44", "CD25", "(DN2)", "and", "CD44", "CD25", "(DN3).", "TCR", "rearrangements", "are", "initiated", "in", "the", "CD44", "CD25", "DN2", "stage.", "When", "these", "rearrangements", "are", "successful,", "the", "translated", "TCR", "protein", "forms", "a", "pre-TCR", "complex", "with", "the", "pT", "chain", "and", "signals", "emanating", "from", "this", "receptor", "result", "in", "survival", "and", "proliferation", "of", "TCR", "-", "expressing", "cells", "(2,", "3).", "As", "a", "consequence", "of", "-selection,", "the", "CD44", "CD25", "cells", "lose", "CD25,", "acquire", "CD2", "and", "CD5", "(4),", "and", "rapidly", "differentiate", "through", "an", "intermediate", "CD4", "CD8", ",", "immature", "(TCRlow)", "single", "positive", "(ISP)", "stage,", "to", "the", "CD4", "CD8", "double", "positive", "(DP)", "stage.", "In", "the", "early", "stages", "of", "T", "cell", "development,", "these", "cells", "go", "through", "two", "waves", "of", "proliferation:", "one", "mediated", "by", "the", "cytokines", "IL-7", "and", "stem", "cell", "factor", "and", "the", "other", "by", "trigger-", "ing", "of", "the", "pre-TCR", "complex.", "IL-7", "and", "stem", "cell", "factor", "control", "the", "proliferation", "of", "the", "two", "first", "stages,", "DN1", "and", "DN2,", "and", "survival", "of", "the", "DN3", "cells", "(5–7).", "Pre-TCR", "trig-", "gering", "induces", "a", "second", "wave", "of", "extensive", "proliferation", "of", "T.J.", "Hagenbeek", "and", "M.", "Naspetti", "contributed", "equally", "to", "this", "work.", "Address", "correspondence", "to", "Hergen", "Spits,", "Dept.", "of", "Cell", "Biology", "and", "Histology,", "University", "of", "Amsterdam,", "Academic", "Medical", "Center,", "Meiberg-", "dreef", "15,", "1105", "AZ,", "Amsterdam.", "Phone:", "31-20-5664977;", "Fax:", "31-20-", "6974156;", "email:", "hergen.spits@amc.uva.nl", "Abbreviations", "used", "in", "this", "paper:", "DN,", "double", "negative;", "DP,", "double", "positive;", "ISP,", "immature", "single", "positive;", "Itk,", "IL-2–inducible", "T", "cell", "kinase;", "PDK-1,", "phosphoinositide-dependent", "kinase-1;", "PI-3K,", "phosphatidylinositol", "3", "kinase;", "PKB,", "protein", "kinase", "B;", "PTEN,", "phosphatase", "and", "tensin", "homologue", "deleted", "on", "chromosome", "10;", "SP,", "single", "positive.", "883", "J.", "Exp.", "Med.", "©", "The", "Rockefeller", "University", "Press", "•", "0022-1007/2004/10/883/12", "$8.00", "Volume", "200,", "Number", "7,", "October", "4,", "2004", "883–894", "http://www.jem.org/cgi/doi/10.1084/jem.20040495" ]

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[ "Int", "J", "Emerg", "Med", "(2010)", "3:85–90", "DOI", "10.1007/s12245-010-0159-y", "ORIGINAL", "RESEARCH", "ARTICLE", "Value", "of", "the", "swimming", "position", "and", "arm", "traction", "in", "visualizing", "the", "cervicothoracic", "junction", "over", "the", "standard", "lateral", "cervical", "X-ray", "Aydin", "Toksoy", "&", "Firat", "Bektas", "&", "Cenker", "Eken", "&", "Kaan", "Ceken", "&", "Yildiray", "Cete", "Received:", "13", "May", "2009", "/", "Accepted:", "11", "January", "2010", "/", "Published", "online:", "23", "March", "2010", "#", "Springer-Verlag", "London", "Ltd", "2010", "Abstract", "Background", "The", "cervicothoracic", "junction", "(CTJ)", "is", "often", "inadequately", "visualized", "on", "lateral", "cervical", "X-rays", "due", "to", "anatomic", "variations", "and", "technical", "factors.", "Aims", "The", "aim", "of", "this", "study", "was", "to", "investigate", "whether", "the", "swimmer’s", "view", "and", "arm", "traction", "could", "enhance", "the", "image", "field", "on", "the", "standard", "lateral", "cervical", "(SLC)", "X-ray.", "Methods", "The", "study", "was", "conducted", "in", "a", "university", "hospital", "in", "October", "2007", "with", "40", "volunteers.", "SLC", "X-ray,", "lateral", "cervical", "X-ray", "in", "the", "swimming", "position,", "and", "lateral", "cervical", "X-ray", "with", "arm", "traction", "were", "performed", "in", "the", "supine", "position.", "The", "enhancements", "in", "the", "image", "fields", "were", "analyzed.", "Results", "There", "was", "a", "statistically", "significant", "difference", "for", "the", "increases", "in", "the", "view", "of", "cervical", "spines", "between", "SLC", "X-ray", "(12.60±", "7.48)", "and", "either", "lateral", "cervical", "X-ray", "with", "arm", "traction", "(21.73±9.78;", "p=0.000)", "or", "in", "the", "swimming", "position", "(21.20±", "14.19;", "p=0.001).", "Both", "arm", "traction", "and", "swimming", "position", "increased", "the", "field", "of", "view", "by", "approximately", "9", "mm.", "Increased", "visualization", "of", "the", "cervical", "spine", "occurred", "for", "24", "The", "views", "expressed", "in", "this", "paper", "are", "those", "of", "the", "author(s)", "and", "not", "those", "of", "the", "editors,", "editorial", "board", "or", "publisher.", "A.", "Toksoy", ":", "F.", "Bektas", ":", "C.", "Eken", "(*)", ":", "Y.", "Cete", "Department", "of", "Emergency", "Medicine,", "Akdeniz", "University", "Medical", "Faculty,", "07059", "Antalya,", "Turkey", "e-mail:", "cenkereken@akdeniz.edu.tr", "F.", "Bektas", "e-mail:", "fbektas@akdeniz.edu.tr", "Y.", "Cete", "e-mail:", "ycete@akdeniz.edu.tr", "K.", "Ceken", "Department", "of", "Radiology,", "Akdeniz", "University", "Medical", "Faculty,", "07059", "Antalya,", "Turkey", "of", "the", "40", "participants", "using", "the", "arm", "traction", "view", "(60.0%)", "and", "23", "participants", "(57.5%)", "using", "the", "swimming", "position", "view—results", "found", "to", "be", "statistically", "similar", "according", "to", "the≥1/3", "caudal", "vertebral", "height", "visualized", "(p=0.902).", "Using", "the", "lateral", "cervical", "X-ray", "view,", "the", "number", "of", "cervical", "vertebrae", "visualized", "differed", "according", "to", "body", "mass", "index", "(BMI)—seven", "cervical", "vertebrae", "were", "visualized", "in", "partic-", "ipants", "with", "a", "BMI", "<25", "and", "six", "vertebrae", "were", "visualized", "in", "participants", "with", "a", "BMI", "≥25", "(p", "=0.007).", "Conclusion", "Lateral", "cervical", "X-rays", "with", "arm", "traction", "and", "swimming", "position", "enhance", "the", "view", "of", "SLC", "X-rays.", "An", "initial", "SLC", "X-ray", "including", "the", "lower", "third", "of", "the", "cervical", "spine", "(with", "C7),", "arm", "traction,", "and", "swimming", "position", "may", "be", "beneficial", "in", "visualizing", "the", "CTJ.", "However,", "patients", "with", "an", "increased", "BMI", "are", "unlikely", "to", "benefit", "from", "all", "three", "methods.", "Keywords", "Lateral", "cervical", "X-ray", ".", "Arm", "traction", ".", "Swimming", "position", ".", "Body", "mass", "index", ".", "Trauma", "Introduction", "For", "patients", "presenting", "with", "multiple", "trauma", "to", "the", "emergency", "department", "(ED),", "advanced", "trauma", "life", "support", "(ATLS)", "guidelines", "recommend", "that", "lateral", "and", "anteroposterior", "cervical", "X-rays", "should", "demonstrate", "a", "complete", "visualization", "of:", "(1)", "all", "cervical", "vertebrae,", "(2)", "the", "cervicothoracic", "junction", "(CTJ),", "and", "(3)", "the", "first", "thoracic", "vertebra", "[1].", "The", "misdiagnosis", "of", "cervical", "spine", "injury", "may", "have", "terrible", "consequences,", "particularly", "in", "the", "cervicothoracic", "region,", "where", "9–18%", "of", "cervical", "spine", "injuries", "are", "seen", "[2–4].", "However,", "the", "CTJ", "is", "often", "inadequately", "visualized", "on", "lateral", "cervical", "X-rays", "due", "to", "anatomic", "variations", "and", "technical", "factors.", "Body", "mass", "index", "(BMI)", "and", "the", "length", "of" ]

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[ "Alzheimer’s", "Disease-Linked", "Mutations", "in", "Presenilin-1", "Result", "in", "a", "Drastic", "Loss", "of", "Activity", "in", "Purified", "c-Secretase", "Complexes", "Matthias", "Cacquevel,", "Lore`", "ne", "Aeschbach,", "Jemila", "Houacine,", "Patrick", "C.", "Fraering*", "E´cole", "Polytechnique", "Fe´de´rale", "de", "Lausanne,", "Brain", "Mind", "Institute,", "Laboratory", "of", "Molecular", "and", "Cellular", "Biology", "of", "Alzheimer’s", "Disease,", "Lausanne,", "Switzerland", "Abstract", "Background:", "Mutations", "linked", "to", "early", "onset,", "familial", "forms", "of", "Alzheimer’s", "disease", "(FAD)", "are", "found", "most", "frequently", "in", "PSEN1,", "the", "gene", "encoding", "presenilin-1", "(PS1).", "Together", "with", "nicastrin", "(NCT),", "anterior", "pharynx-defective", "protein", "1", "(APH1),", "and", "presenilin", "enhancer", "2", "(PEN2),", "the", "catalytic", "subunit", "PS1", "constitutes", "the", "core", "of", "the", "c-secretase", "complex", "and", "contributes", "to", "the", "proteolysis", "of", "the", "amyloid", "precursor", "protein", "(APP)", "into", "amyloid-beta", "(Ab)", "peptides.", "Although", "there", "is", "a", "growing", "consensus", "that", "FAD-linked", "PS1", "mutations", "affect", "Ab", "production", "by", "enhancing", "the", "Ab1–42/Ab1–40", "ratio,", "it", "remains", "unclear", "whether", "and", "how", "they", "affect", "the", "generation", "of", "APP", "intracellular", "domain", "(AICD).", "Moreover,", "controversy", "exists", "as", "to", "how", "PS1", "mutations", "exert", "their", "effects", "in", "different", "experimental", "systems,", "by", "either", "increasing", "Ab1–42", "production,", "decreasing", "Ab1–40", "production,", "or", "both.", "Because", "it", "could", "be", "explained", "by", "the", "heterogeneity", "in", "the", "composition", "of", "c-secretase,", "we", "purified", "to", "homogeneity", "complexes", "made", "of", "human", "NCT,", "APH1aL,", "PEN2,", "and", "the", "pathogenic", "PS1", "mutants", "L166P,", "DE9,", "or", "P436Q.", "Methodology/Principal", "Findings:", "We", "took", "advantage", "of", "a", "mouse", "embryonic", "fibroblast", "cell", "line", "lacking", "PS1", "and", "PS2", "to", "generate", "different", "stable", "cell", "lines", "overexpressing", "human", "c-secretase", "complexes", "with", "different", "FAD-linked", "PS1", "mutations.", "A", "multi-step", "affinity", "purification", "procedure", "was", "used", "to", "isolate", "semi-purified", "or", "highly", "purified", "c-secretase", "complexes.", "The", "functional", "characterization", "of", "these", "complexes", "revealed", "that", "all", "PS1", "FAD-linked", "mutations", "caused", "a", "loss", "of", "c-secretase", "activity", "phenotype,", "in", "terms", "of", "Ab1–40,", "Ab1–42", "and", "APP", "intracellular", "domain", "productions", "in", "vitro.", "Conclusion/Significance:", "Our", "data", "support", "the", "view", "that", "PS1", "mutations", "lead", "to", "a", "strong", "c-secretase", "loss-of-function", "phenotype", "and", "an", "increased", "Ab1–42/Ab1–40", "ratio,", "two", "mechanisms", "that", "are", "potentially", "involved", "in", "the", "pathogenesis", "of", "Alzheimer’s", "disease.", "Citation:", "Cacquevel", "M,", "Aeschbach", "L,", "Houacine", "J,", "Fraering", "PC", "(2012)", "Alzheimer’s", "Disease-Linked", "Mutations", "in", "Presenilin-1", "Result", "in", "a", "Drastic", "Loss", "of", "Activity", "in", "Purified", "c-Secretase", "Complexes.", "PLoS", "ONE", "7(4):", "e35133.", "doi:10.1371/journal.pone.0035133", "Editor:", "Stefano", "L.", "Sensi,", "University", "G.", "D’Annunzio,", "Italy", "Received", "February", "20,", "2012;", "Accepted", "March", "13,", "2012;", "Published", "April", "18,", "2012", "Copyright:", "2012", "Cacquevel", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "the", "Swiss", "National", "Foundation", "(to", "and", "LA", "and", "PCF;", "grant", "31003A_134938/1)", "and", "the", "National", "Centre", "for", "Competence", "in", "Research", "(‘‘Neuronal", "Plasticity", "and", "Repair’’", "(to", "JH", "and", "PCF)),", "and", "the", "Strauss", "foundation", "(to", "PCF).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "patrick.fraering@epfl.ch", "Introduction", "Since", "their", "discovery", "in", "1995", "and", "their", "association", "with", "early", "onset", "familial", "Alzheimer’s", "disease", "(FAD)", "[1,2],", "the", "presenilin", "genes", "PSEN1", "and", "PSEN2", "have", "been", "widely", "studied,", "and", "the", "complexity", "of", "their", "biological", "role", "is", "becoming", "increasingly", "evident.", "PSEN1", "and", "PSEN2", "encode", "transmembrane", "proteins", "PS1", "and", "PS2,", "respectively,", "that", "constitute", "the", "catalytic", "core", "of", "c-secretase,", "the", "founding", "member", "of", "an", "emerging", "class", "of", "unconventional,", "Intramembrane-Cleaving", "Proteases", "(I-CLiPs)", "[3].", "Active", "c-secre-", "tase", "is", "a", "multiprotein", "complex", "composed", "of", "PS1", "or", "PS2", "together", "with", "nicastrin", "(NCT),", "the", "anterior", "pharynx-defective", "protein", "1", "(APH1),", "and", "the", "presenilin", "enhancer", "2", "(PEN2).", "Experimental", "evidence", "such", "as", "the", "binding", "of", "transition-state", "analogue", "c-", "secretase", "inhibitors", "to", "PS1", "[4],", "as", "well", "as", "the", "abolishment", "of", "c-", "secretase", "activity", "when", "PS1", "lacks", "the", "aspartate", "residues", "critical", "for", "proteolysis", "[4,5,6],", "have", "confirmed", "that", "presenilins", "harbour", "the", "active", "site", "of", "the", "enzymatic", "complex.", "PS1", "and", "PS2", "play", "fundamental", "roles", "in", "cell", "signalling", "as", "part", "of", "the", "c-secretase", "complex.", "The", "latter", "cleaves", "numerous", "type-I", "membrane", "proteins", "in", "their", "transmembrane", "domain", "[7],", "releasing", "their", "corresponding", "intracellular", "domains,", "which", "are", "capable", "of", "influencing", "gene", "expression.", "For", "some", "substrates", "like", "NOTCH1", "or", "ERBB4,", "the", "c-secretase", "cleavage", "is", "essential", "for", "their", "biological", "function,", "whereas", "for", "other", "substrates", "like", "DCC", "or", "NEUREXIN-", "3b", "[8],", "the", "possible", "role", "of", "the", "cleavage", "in", "signalling", "events", "has", "not", "been", "formally", "established", "(see", "[9]", "for", "a", "review).", "The", "amyloid", "precursor", "protein", "(APP)", "is", "processed", "by", "the", "successive", "actions", "of", "b-", "secretase", "(BACE1)", "and", "c-secretase,", "generating", "amyloid-beta", "peptides", "(Ab)", "of", "different", "lengths,", "ranging", "from", "37", "to", "46", "amino", "acids", "[10].", "Cleavage", "of", "the", "APP", "C-terminal", "fragments", "(APP-CTFs)", "by", "c-secretase", "also", "releases", "the", "APP", "intracellular", "domain", "(AICD),", "which", "has", "been", "recently", "involved", "in", "the", "regulation", "of", "brain", "ApoE", "expression,", "a", "major", "genetic", "determinant", "of", "AD,", "and", "in", "cholesterol", "metabolism", "[11].", "In", "addition,", "PS1", "has", "been", "shown", "to", "interact", "with", "a", "growing", "list", "of", "proteins", "that", "modulate", "c-secretase", "activity", "[9,12,13,14].", "PLoS", "ONE", "|", "www.plosone.org", "1", "April", "2012", "|", "Volume", "7", "|", "Issue", "4", "|", "e35133" ]

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[ "Sensors", "2011,", "11,", "7992;", "doi:10.3390/s110807992", "OPEN", "ACCESS", "sensors", "ISSN", "1424-8220", "www.mdpi.com/journal/sensors", "Retraction", "Shu-Kun", "Lin", "Retraction:", "Eldefrawy,", "M.H.;", "Khan,", "M.K.;", "Alghathbar,", "K.;", "Tolba,", "A.S.;", "Kim,", "K.J.", "Authenticated", "Key", "Agreement", "with", "Rekeying", "for", "Secured", "Body", "Sensor", "Networks.", "Sensors", "2011,", "11,", "5835-5849.", "MDPI", "AG,", "Postfach,", "CH-4005", "Basel,", "Switzerland;", "Office:", "Kandererstrasse", "25,", "4057", "Basel,", "Switzerland;", "E-Mail:", "lin@mdpi.com", "Received:", "8", "August", "2011", "/", "Published:", "15", "August", "2011", "It", "has", "been", "brought", "to", "our", "attention", "by", "a", "reader", "of", "Sensors", "that", "substantial", "portions", "of", "this", "article", "[1]", "have", "been", "copied", "from", "earlier", "publications", "without", "credit.", "After", "confirming", "this", "plagiarism", "with", "the", "authors,", "we", "have", "determined", "that", "indeed", "this", "manuscript", "clearly", "violates", "our", "policy", "on", "originality", "of", "all", "material", "submitted", "for", "publication", "and", "the", "generally", "accepted", "ethics", "of", "scientific", "publication.", "Consequently,", "the", "Editorial", "Team", "and", "Publisher", "have", "determined", "that", "it", "should", "be", "retracted.", "We", "apologize", "for", "any", "inconvenience", "this", "may", "cause.", "References", "1.", "Eldefrawy,", "M.H.;", "Khan,", "M.K.;", "Alghathbar,", "K.;", "Tolba,", "A.S.;", "Kim,", "K.J.", "Authenticated", "Key", "Agreement", "with", "Rekeying", "for", "Secured", "Body", "Sensor", "Networks.", "Sensors", "2011,", "11,", "5835-5849.", "©", "2011", "by", "the", "authors;", "licensee", "MDPI,", "Basel,", "Switzerland.", "This", "article", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "and", "conditions", "of", "the", "Creative", "Commons", "Attribution", "license", "(http://creativecommons.org/licenses/by/3.0/)." ]

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[ "Kuijpers1*", "Abstract", "Stabilizing", "Role", "of", "Platelet", "P2Y12", "Receptors", "in", "Shear-", "Dependent", "Thrombus", "Formation", "on", "Ruptured", "Plaques", "Reyhan", "Nergiz-Unal1,", "Judith", "M.", "E.", "M.", "Cosemans1,", "Marion", "A.", "H.", "Feijge1,", "Paola", "E.", "J.", "van", "der", "Meijden", "1", ",", "Robert", "F.", "Storey2,", "J.", "J.", "J.", "van", "Giezen", "3", ",", "Mirjam", "G.", "A.", "oude", "Egbrink4,", "Johan", "W.", "M.", "Heemskerk1,", "Marijke", "J.", "E.", "1", "Department", "of", "Biochemistry,", "Cardiovascular", "Research", "Institute", "Maastricht", "(CARIM),", "Maastricht", "University,", "Maastricht,", "The", "Netherlands,", "2", "Department", "of", "Cardiovascular", "Science,", "University", "of", "Sheffield,", "Sheffield,", "United", "Kingdom,", "3", "AstraZeneca", "R&D", "Mo¨", "lndal,", "Mo¨", "lndal,", "Sweden,", "4", "Department", "of", "Physiology,", "Cardiovascular", "Research", "Institute", "Maastricht", "(CARIM),", "Maastricht", "University,", "Maastricht,", "The", "Netherlands", "Background:", "In", "most", "models", "of", "experimental", "thrombosis,", "healthy", "blood", "vessels", "are", "damaged.", "This", "results", "in", "the", "formation", "of", "a", "platelet", "thrombus", "that", "is", "stabilized", "by", "ADP", "signaling", "via", "P2Y12", "receptors.", "However,", "such", "models", "do", "not", "predict", "involvement", "of", "P2Y12", "in", "the", "clinically", "relevant", "situation", "of", "thrombosis", "upon", "rupture", "of", "atherosclerotic", "plaques.", "We", "investigated", "the", "role", "of", "P2Y12", "in", "thrombus", "formation", "on", "(collagen-containing)", "atherosclerotic", "plaques", "in", "vitro", "and", "in", "vivo,", "by", "using", "a", "novel", "mouse", "model", "of", "atherothrombosis.", "Methodology:", "Plaques", "in", "the", "carotid", "arteries", "from", "Apoe2/2", "mice", "were", "acutely", "ruptured", "by", "ultrasound", "treatment,", "and", "the", "thrombotic", "process", "was", "monitored", "via", "intravital", "fluorescence", "microscopy.", "Thrombus", "formation", "in", "vitro", "was", "assessed", "in", "mouse", "and", "human", "blood", "perfused", "over", "collagen", "or", "plaque", "material", "under", "variable", "conditions", "of", "shear", "rate", "and", "coagulation.", "Effects", "of", "two", "reversible", "P2Y12", "blockers,", "ticagrelor", "(AZD6140)", "and", "cangrelor", "(AR-C69931MX),", "were", "investigated.", "Principal", "Findings:", "Acute", "plaque", "rupture", "by", "ultrasound", "treatment", "provoked", "rapid", "formation", "of", "non-occlusive", "thrombi,", "which", "were", "smaller", "in", "size", "and", "unstable", "in", "the", "presence", "of", "P2Y12", "blockers.", "In", "vitro,", "when", "mouse", "or", "human", "blood", "was", "perfused", "over", "collagen", "or", "atherosclerotic", "plaque", "material,", "blockage", "or", "deficiency", "of", "P2Y12", "reduced", "the", "thrombi", "and", "increased", "embolization", "events.", "These", "P2Y12", "effects", "were", "present", "at", "shear", "rates", ".500", "s21,", "and", "they", "persisted", "in", "the", "presence", "of", "coagulation.", "P2Y12-dependent", "thrombus", "stabilization", "was", "accompanied", "by", "increased", "fibrin(ogen)", "binding.", "Conclusions/Significance:", "Platelet", "P2Y12", "receptors", "play", "a", "crucial", "role", "in", "the", "stabilization", "of", "thrombi", "formed", "on", "atherosclerotic", "plaques.", "This", "P2Y12", "function", "is", "restricted", "to", "high", "shear", "flow", "conditions,", "and", "is", "preserved", "in", "the", "presence", "of", "coagulation.", "Citation:", "Nergiz-Unal", "R,", "Cosemans", "JMEM,", "Feijge", "MAH,", "van", "der", "Meijden", "PEJ,", "Storey", "RF,", "et", "al.", "(2010)", "Stabilizing", "Role", "of", "Platelet", "P2Y12", "Receptors", "in", "Shear-", "Dependent", "Thrombus", "Formation", "on", "Ruptured", "Plaques.", "PLoS", "ONE", "5(4):", "e10130.", "doi:10.1371/journal.pone.0010130", "Editor:", "Yu", "Wang,", "Hong", "Kong", "University,", "Hong", "Kong", "Received", "October", "6,", "2009;", "Accepted", "March", "12,", "2010;", "Published", "April", "12,", "2010", "Copyright:", "2010", "Nergiz-Unal", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "Partial", "financial", "support", "for", "the", "conductance", "of", "this", "study", "was", "provided", "by", "AstraZeneca.", "Support", "is", "acknowledged", "from", "the", "Hacettepe", "University", "(Ankara,", "Turkey),", "the", "Netherlands", "Organization", "for", "Scientific", "Research", "(11.400.0076)", "and", "the", "Netherlands", "Heart", "Foundation", "(2005B079).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "J.J.J.", "van", "Giezen", "is", "an", "employee", "of", "AstraZeneca.", "Partial", "financial", "support", "for", "the", "conductance", "of", "this", "study", "was", "provided", "by", "AstraZeneca", "who", "own", "the", "patent", "for", "ticagrelor.", "This", "does", "not", "alter", "the", "authors’", "adherence", "to", "all", "the", "PLoS", "ONE", "policies", "on", "sharing", "data", "and", "materials,", "as", "detailed", "online", "in", "the", "guide", "for", "authors.", "*", "E-mail:", "Marijke.Kuijpers@bioch.unimaas.nl", "Introduction", "Rupture", "of", "an", "atherosclerotic", "plaque", "and", "occlusive", "arterial", "thrombus", "formation", "is", "the", "major", "cause", "of", "acute", "cardiovascular", "incidents", "and", "deaths", "in", "the", "Western", "countries", "[1].", "The", "development", "of", "a", "thrombus", "is", "a", "complex", "and", "dynamic", "process,", "involving", "platelet", "aggregation,", "generation", "of", "thrombin", "and", "formation", "of", "a", "network", "of", "fibrin,", "to", "strengthen", "the", "platelet", "aggregate", "and", "stabilize", "the", "thrombus", "[2,3].", "In", "vivo", "mouse", "models", "of", "experimental", "thrombosis", "have", "indicated", "a", "major", "role", "of", "platelet", "receptors", "in", "the", "process", "of", "thrombus", "formation", "and", "stabilization", "[4].", "However,", "the", "studies", "have", "been", "carried", "out", "by", "damaging", "healthy", "mouse", "arteries", "in", "an", "artificial", "way,", "e.g.", "by", "laser-induced", "tissue", "ablation,", "free", "radical-generating", "agents", "or", "mechanical", "disruption.", "Thrombus", "formation", "in", "diseased,", "atherosclerotic", "arteries", "following", "plaque", "rupture", "has", "hardly", "been", "investigated.", "Ruptured", "atherosclerotic", "plaques", "expose", "several", "platelet-adhe-", "sive", "and", "-activating", "components,", "such", "as", "collagen", "types", "I", "and", "III,", "von", "Willebrand", "factor", "(VWF),", "lysophosphatidic", "acid,", "thrombos-", "pondin,", "fibronectin,", "vitronectin,", "fibrin/fibrinogen", "and", "oxidized", "low", "density", "lipoprotein", "[5,6,7,8,9,10].", "In", "addition,", "plaques", "contain", "tissue", "factor", "which,", "upon", "de-encryption,", "activates", "the", "extrinsic", "coagulation", "system", "[5],", "while", "the", "intrinsic", "system", "of", "factor", "XII", "activation", "is", "triggered", "via", "collagen", "[11].", "To", "which", "extent", "each", "of", "these", "plaque", "components", "contribute", "to", "thrombus", "formation", "is", "unclear,", "though", "the", "platelet-activating", "roles", "of", "VWF", "and", "collagen", "are", "well-described", "[1].", "Collagen-bound", "VWF", "mediates", "the", "initial", "tethering", "and", "transient", "adhesion", "of", "platelets", "via", "glycoprotein", "PLoS", "ONE", "|", "www.plosone.org", "1", "April", "2010", "|", "Volume", "5", "|", "Issue", "4", "|", "e10130" ]

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[ "Molecular", "Vision", "2010;", "16:252-271", "<http://www.molvis.org/molvis/v16/a32>", "Received", "12", "July", "2009", "|", "Accepted", "10", "February", "2010", "|", "Published", "17", "February", "2010", "©", "2010", "Molecular", "Vision", "Temporal", "ChIP-on-Chip", "of", "RNA-Polymerase-II", "to", "detect", "novel", "gene", "activation", "events", "during", "photoreceptor", "maturation", "Padmaja", "Tummala,", "Raghuveer", "S.", "Mali,", "Eduardo", "Guzman,", "Xiao", "Zhang,", "Kenneth", "P.", "Mitton", "(The", "first", "two", "authors", "contributed", "equally", "to", "this", "work.)", "Eye", "Research", "Institute,", "Oakland", "University,", "Rochester,", "MI", "Purpose:", "During", "retinal", "development,", "post-mitotic", "neural", "progenitor", "cells", "must", "activate", "thousands", "of", "genes", "to", "complete", "synaptogenesis", "and", "terminal", "maturation.", "While", "many", "of", "these", "genes", "are", "known,", "others", "remain", "beyond", "the", "sensitivity", "of", "expression", "microarray", "analysis.", "Some", "of", "these", "elusive", "gene", "activation", "events", "can", "be", "detected", "by", "mapping", "changes", "in", "RNA", "polymerase-II", "(Pol-II)", "association", "around", "transcription", "start", "sites.", "Methods:", "High-resolution", "(35", "bp)", "chromatin", "immunoprecipitation", "(ChIP)-on-chip", "was", "used", "to", "map", "changes", "in", "Pol-II", "binding", "surrounding", "26,000", "gene", "transcription", "start", "sites", "during", "photoreceptor", "maturation", "of", "the", "mouse", "neural", "retina,", "comparing", "postnatal", "age", "25", "(P25)", "to", "P2.", "Coverage", "was", "10–12", "kb", "per", "transcription", "start", "site,", "including", "2.5", "kb", "downstream.", "Pol-II-active", "regions", "were", "mapped", "to", "the", "mouse", "genomic", "DNA", "sequence", "by", "using", "computational", "methods", "(Tiling", "Analysis", "Software-TAS", "program),", "and", "the", "ratio", "of", "maximum", "Pol-II", "binding", "(P25/P2)", "was", "calculated", "for", "each", "gene.", "A", "validation", "set", "of", "36", "genes", "(3%),", "representing", "a", "full", "range", "of", "Pol-II", "signal", "ratios", "(P25/P2),", "were", "examined", "with", "quantitative", "ChIP", "assays", "for", "transcriptionally", "active", "Pol-II.", "Gene", "expression", "assays", "were", "also", "performed", "for", "19", "genes", "of", "the", "validation", "set,", "again", "on", "independent", "samples.", "FLT-3", "Interacting", "Zinc-finger-1", "(FIZ1),", "a", "zinc-finger", "protein", "that", "associates", "with", "active", "promoter", "complexes", "of", "photoreceptor-specific", "genes,", "provided", "an", "additional", "ChIP", "marker", "to", "highlight", "genes", "activated", "in", "the", "mature", "neural", "retina.", "To", "demonstrate", "the", "use", "of", "ChIP-on-chip", "predictions", "to", "find", "novel", "gene", "activation", "events,", "four", "additional", "genes", "were", "selected", "for", "quantitative", "PCR", "analysis", "(qRT–PCR", "analysis);", "these", "four", "genes", "have", "human", "homologs", "located", "in", "unidentified", "retinal", "disease", "regions:", "Solute", "carrier", "family", "25", "member", "33", "(Slc25a33),", "Lysophosphatidylcholine", "acyltransferase", "1", "(Lpcat1),", "Coiled-coil", "domain-containing", "126", "(Ccdc126),", "and", "ADP-ribosylation", "factor-like", "4D", "(Arl4d).", "Results:", "ChIP-on-chip", "Pol-II", "peak", "signal", "ratios", ">1.8", "predicted", "increased", "amounts", "of", "transcribing", "Pol-II", "and", "increased", "expression", "with", "an", "estimated", "97%", "accuracy,", "based", "on", "analysis", "of", "the", "validation", "gene", "set.", "Using", "this", "threshold", "ratio,", "1,101", "genes", "were", "predicted", "to", "experience", "increased", "binding", "of", "Pol-II", "in", "their", "promoter", "regions", "during", "terminal", "maturation", "of", "the", "neural", "retina.", "Over", "800", "of", "these", "gene", "activations", "were", "additional", "to", "those", "previously", "reported", "by", "microarray", "analysis.", "Slc25a33,", "Lpcat1,", "Ccdc126,", "and", "Arl4d", "increased", "expression", "significantly", "(p<0.001)", "during", "photoreceptor", "maturation.", "Expression", "of", "all", "four", "genes", "was", "diminished", "in", "adult", "retinas", "lacking", "rod", "photoreceptors", "(Rd1", "mice)", "compared", "to", "normal", "retinas", "(90%", "loss", "for", "Ccdc126", "and", "Arl4d).", "For", "rhodopsin", "(Rho),", "a", "marker", "of", "photoreceptor", "maturation,", "two", "regions", "of", "maximum", "Pol-II", "signal", "corresponded", "to", "the", "upstream", "rhodopsin", "enhancer", "region", "and", "the", "rhodopsin", "proximal", "promoter", "region.", "Conclusions:", "High-resolution", "maps", "of", "Pol-II", "binding", "around", "transcription", "start", "sites", "were", "generated", "for", "the", "postnatal", "mouse", "retina;", "which", "can", "predict", "activation", "increases", "for", "a", "specific", "gene", "of", "interest.", "Novel", "gene", "activation", "predictions", "are", "enriched", "for", "biologic", "functions", "relevant", "to", "vision,", "neural", "function,", "and", "chromatin", "regulation.", "Use", "of", "the", "data", "set", "to", "detect", "novel", "activation", "increases", "was", "demonstrated", "by", "expression", "analysis", "for", "several", "genes", "that", "have", "human", "homologs", "located", "within", "unidentified", "retinal", "disease", "regions:", "Slc25a33,", "Lpcat1,", "Ccdc126,", "and", "Arl4d.", "Analysis", "of", "photoreceptor-deficient", "retinas", "indicated", "that", "all", "four", "genes", "are", "expressed", "in", "photoreceptors.", "Genome-wide", "maps", "of", "Pol-II", "binding", "were", "developed", "for", "visual", "access", "in", "the", "University", "of", "California,", "Santa", "Cruz", "(UCSC)", "Genome", "Browser", "and", "its", "eye-centric", "version", "EyeBrowse", "(National", "Eye", "Institute-NEI).", "Single", "promoter", "resolution", "of", "Pol-II", "distribution", "patterns", "suggest", "the", "Rho", "enhancer", "region", "and", "the", "Rho", "proximal", "promoter", "region", "become", "closely", "associated", "with", "the", "activated", "gene’s", "promoter", "complex.", "Cell-specific", "gene", "expression", "is", "required", "for", "the", "specialized", "functions", "of", "an", "adult", "tissue.", "Depending", "on", "the", "tissue", "of", "interest,", "we", "may", "know", "about", "hundreds", "of", "the", "relevant", "Correspondence", "to:", "Kenneth", "P.", "Mitton,", "Associate", "Professor", "of", "Biomedical", "Sciences,", "Eye", "Research", "Institute,", "Room", "412,", "Dodge", "Hall,", "Oakland", "University,", "Rochester,", "MI,", "48309-4401;", "Phone:", "(248)", "370-2079;", "FAX:", "(248)", "370-2006;", "email:", "mitton@oakland.edu", "genes", "and", "even", "several", "key", "transcription", "factors", "that", "regulate", "their", "expression.", "Unfortunately,", "our", "knowledge", "is", "not", "complete", "regarding", "the", "number", "of", "genes", "that", "must", "become", "active", "or", "their", "identities.", "Chromatin", "immunoprecipitation", "(ChIP)-on-chip", "analysis", "of", "RNA", "polymerase-II", "(Pol-II)", "binding", "in", "gene", "promoters", "has", "revealed", "additional", "and", "novel", "gene", "activation", "changes", "in", "cultured", "cells,", "including", "embryonic", "252" ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "2", "(Croconato-j", "O,O0)bis(1,10-phenanthro-", "2", "line-j", "N,N0)zinc(II)", "Hongyu", "Chen,a*", "Ping", "Li,a", "Lihua", "Dong,a", "Xiaohui", "Zhua", "and", "Qi", "Fangb", "aSchool", "of", "Chemistry", "and", "Chemical", "Engineering,", "TaiShan", "Medical", "University,", "Tai’an", "271016,", "People’s", "Republic", "of", "China,", "and", "bState", "Key", "Laboratory", "of", "Crystal", "Materials,", "Shandong", "University,", "Jinan", "250100,", "Shandong", "Province,", "People’s", "Republic", "of", "China", "Correspondence", "e-mail:", "binboll@126.com", "Received", "5", "August", "2008;", "accepted", "15", "October", "2008", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "293", "K;", "mean", "(C–C)", "=", "0.003", "A˚;", "R", "factor", "=", "0.029;", "wR", "factor", "=", "0.096;", "data-to-parameter", "ratio", "=", "14.7.", "In", "the", "title", "compound,", "[Zn(C5O5)(C12H8N2)2],", "the", "Zn", "atom", "is", "in", "a", "slightly", "distorted", "octahedral", "environment.", "The", "molecule", "lies", "across", "a", "twofold", "rotation", "axis,", "around", "which", "two", "1,10-", "phenanthroline", "ligands", "are", "arranged.", "There", "are", "short", "contacts", "between", "the", "1,10-phenanthroline", "groups", "and", "the", "O", "atoms", "of", "the", "croconate", "ligand,", "which", "probably", "stabilize", "the", "crystal", "structure", "via", "weak", "C—H", "O", "interactions.", "Related", "literature", "For", "related", "literature,", "see:", "Braga", "et", "al.", "(2002);", "Carranza", "et", "al.", "(2004);", "Castro", "et", "al.", "(1992,", "2002);", "Chen", "et", "al.", "(2005,", "2007,", "2008);", "Faus", "et", "al.", "(1994);", "Maji", "et", "al.", "(2003);", "Seitz", "&", "Imming", "(1992);", "Sletten", "et", "al.", "(1998);", "Wang", "et", "al.", "(2002).", "Experimental", "Crystal", "data", "[Zn(C5O5)(C12H8N2)2]", "Mr", "=", "565.83", "Orthorhombic,", "Pbcn", "a", "=", "12.2605", "(4)", "A˚", "b", "=", "11.0133", "(3)", "A˚", "c", "=", "17.2745", "(5)", "A˚", "V", "=", "2332.55", "(12)", "A˚", "3", "Z", "=", "4", "metal-organic", "compounds", "T", "=", "293", "(2)", "K", "0.28", "0.23", "0.15", "mm", "9769", "measured", "reflections", "2627", "independent", "reflections", "2164", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.019", "179", "parameters", "H-atom", "parameters", "constrained", "max", "=", "0.29", "e", "A˚", "3", "min", "=", "0.32", "e", "A˚", "3", "O1—Zn1", "2.1325", "(14)", "Mo", "K", "radiation", "=", "1.11", "mm", "1", "Data", "collection", "Bruker", "APEXII", "CCD", "area-detector", "diffractometer", "Absorption", "correction:", "multi-scan", "(APEX2;", "Bruker,", "2005)", "Tmin", "=", "0.743,", "Tmax", "=", "0.782", "(expected", "range", "=", "0.805–0.847)", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.029", "wR(F", "2)", "=", "0.096", "S", "=", "1.28", "2627", "reflections", "Table", "1", "Selected", "bond", "lengths", "(A˚", ").", "N1—Zn1", "N2—Zn1", "2.1493", "(15)", "2.1664", "(17)", "Table", "2", "Hydrogen-bond", "geometry", "(A˚", ",", ").", "D—H", "A", "C6—H6", "C11—H11", "O1i", "O3ii", "D—H", "0.93", "0.93", "H", "2.47", "2.55", "A", "D", "A", "3.295", "(2)", "3.147", "(2)", "D—H", "A", "149", "122", "Symmetry", "codes:", "(i)", "x;", "y;", "z", "12;", "(ii)", "x", "12;", "y", "12;", "z", "þ", "32.", "Data", "collection:", "APEX2", "(Bruker,", "2005);", "cell", "refinement:", "APEX2;", "data", "reduction:", "APEX2;", "program(s)", "used", "to", "solve", "structure:", "SIR97", "(Altomare", "et", "al.,", "1999);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "SHELXTL", "(Sheldrick,", "2008);", "software", "used", "to", "prepare", "material", "for", "publication:", "WinGX", "(Farrugia,", "1999).", "This", "work", "was", "supported", "by", "the", "National", "Natural", "Science", "Foundation", "of", "China", "(grant", "No.", "50673054).", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "SG2254).", "References", "Altomare,", "A.,", "Burla,", "M.", "C.,", "Camalli,", "M.,", "Cascarano,", "G.", "L.,", "Giacovazzo,", "C.,", "Guagliardi,", "A.,", "Moliterni,", "A.", "G.", "G.,", "Polidori,", "G.", "&", "Spagna,", "R.", "(1999).", "J.", "Appl.", "Cryst.", "32,", "115–119.", "Braga,", "D.,", "Maini,", "L.", "&", "Grepioni,", "F.", "(2002).", "Chem.", "Eur.", "J.", "8,", "1804–1812.", "Bruker", "(2005).", "APEX2.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Carranza,", "J.,", "Sletten,", "J.,", "Brennan,", "C.,", "Lloret,", "F.,", "Cano,", "J.", "&", "Julve,", "M.", "(2004).", "Dalton", "Trans.", "p.", "3997–4000.", "Castro,", "I.,", "Calatayud,", "M.", "L.,", "Lloret,", "F.,", "Sletten,", "J.", "&", "Julve,", "M.", "(2002).", "J.", "Chem.", "Soc.", "Dalton", "Trans.", "pp.", "2397–2403.", "Castro,", "I.,", "Sletten,", "J.,", "Faus,", "J.,", "Julve,", "M.,", "Journaux,", "Y.,", "Lloret,", "F.", "&", "Alvarez,", "S.", "(1992).", "Inorg.", "Chem.", "31,", "1889–1894.", "Chen,", "H.-F.,", "Chen,", "H.-Y.,", "Chen,", "X.,", "Batsanov,", "A.", "S.", "&", "Fang,", "Q.", "(2008).", "Acta", "Cryst.", "E64,", "m172.", "Chen,", "X.,", "Chen,", "H.-F.,", "Xue,", "G.,", "Chen,", "H.-Y.,", "Yu,", "W.-T.", "&", "Fang,", "Q.", "(2007).", "Acta", "Cryst.", "C63,", "m166–m168.", "Chen,", "H.-Y.,", "Fang,", "Q.,", "Xue,", "G.", "&", "Yu,", "W.-T.", "(2005).", "Acta", "Cryst.", "C61,", "m535–", "m537.", "Farrugia,", "L.", "J.", "(1999).", "J.", "Appl.", "Cryst.", "32,", "837–838.", "Acta", "Cryst.", "(2008).", "E64,", "m1507–m1508", "doi:10.1107/S1600536808033709", "Chen", "et", "al.", "m1507" ]

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[ "2548", "S.", "Mark", "Duffy", "et", "al.", "DOI", "10.1002/eji.200738106", "Eur.", "J.", "Immunol.", "2008.", "38:", "2548–2556", "Engagement", "of", "the", "EP2", "prostanoid", "receptor", "closes", "1", "the", "K", "channel", "KCa3.1", "in", "human", "lung", "mast", "cells", "and", "attenuates", "their", "migration", "S.", "Mark", "Duffy,", "Glenn", "Cruse,", "Sarah", "L.", "Cockerill,", "Chris", "E.", "Brightling", "and", "Peter", "Bradding", "The", "Department", "of", "Infection,", "Immunity", "and", "Inflammation,", "Institute", "for", "Lung", "Health,", "University", "of", "Leicester,", "UK", "Human", "lung", "mast", "cells", "(HLMC)", "express", "the", "Ca21-activated", "K1", "channel", "KCa3.1,", "which", "plays", "a", "crucial", "role", "in", "their", "migration", "to", "a", "variety", "of", "diverse", "chemotactic", "stimuli.", "KCa3.1", "acti-", "vation", "is", "attenuated", "by", "the", "b2-adrenoceptor", "and", "the", "adenosine", "A2A", "receptor", "through", "a", "Gs-coupled", "mechanism", "independent", "of", "cyclic", "AMP.", "Prostaglandin", "E2", "promotes", "degranu-", "lation", "and", "migration", "of", "mouse", "bone", "marrow-derived", "mast", "cells", "through", "the", "Gi-coupled", "EP3", "prostanoid", "receptor,", "and", "induces", "LTC4", "and", "cytokine", "secretion", "from", "human", "cord", "blood-", "derived", "mast", "cells.", "However,", "PGE2", "binding", "to", "the", "Gs-coupled", "EP2", "receptor", "on", "HLMC", "inhibits", "their", "degranulation.", "We", "show", "that", "EP2", "receptor", "engagement", "closes", "KCa3.1", "in", "HLMC.", "The", "EP2", "receptor-specific", "agonist", "butaprost", "was", "more", "potent", "than", "PGE2", "in", "this", "respect,", "and", "the", "effects", "of", "both", "agonists", "were", "reversed", "by", "the", "EP2", "receptor", "antagonist", "AH6809.", "Butaprost", "markedly", "inhibited", "HLMC", "migration", "induced", "by", "chemokine-rich", "airway", "smooth", "muscle-", "conditioned", "media.", "Interestingly,", "PGE2", "alone", "was", "chemotactic", "for", "HLMC", "at", "high", "concen-", "trations", "(1", "lM),", "but", "was", "a", "more", "potent", "chemoattractant", "for", "HLMC", "following", "EP2", "receptor", "blockade.", "Therefore,", "the", "Gs-coupled", "EP2", "receptor", "closes", "KCa3.1", "in", "HLMC", "and", "atten-", "uates", "both", "chemokine-", "and", "PGE2-dependent", "HLMC", "migration.", "EP2", "receptor", "agonists", "with", "KCa3.1", "modulating", "function", "may", "be", "useful", "for", "the", "treatment", "of", "mast", "cell-mediated", "disease.", "Key", "words:", "Chemotaxis", "Ion", "channel", "KCa3.1", "Mast", "cell", "Prostaglandin", "E2", "Introduction", "Mast", "cells", "are", "tissue-dwelling", "cells", "derived", "from", "bone", "marrow", "progenitors.", "They", "are", "present", "in", "all", "organs", "throughout", "the", "human", "body,", "both", "at", "mucosal", "surfaces", "and", "within", "connective", "tissues.", "Mast", "cells", "play", "a", "major", "role", "in", "tissue", "homeostasis,", "host", "defence", "and", "the", "pathophysiology", "of", "many", "diverse", "diseases", "[1].", "These", "include", "pulmonary", "fibrosis,", "rheumatoid", "disease", "and", "atherosclero-", "sis,", "but", "they", "are", "most", "commonly", "associated", "with", "allergic", "disease", "due", "to", "their", "activation", "by", "allergen", "[2].", "In", "many", "diseases", "mast", "cells", "Correspondence:", "Peter", "Bradding", "e-mail:", "pbradding@hotmail.com", "re-locate", "to", "specific", "compartments", "within", "tissue.", "This", "is", "typified", "in", "asthma", "where", "mast", "cells", "migrate", "into", "the", "airway", "epithelium", "[3],", "airway", "smooth", "muscle", "(ASM)", "[4]", "and", "submucosal", "glands", "[5].", "This", "places", "activated", "mast", "cells", "in", "direct", "contact", "with", "these", "dysfunc-", "tional", "airway", "elements,", "allowing", "the", "specific", "delivery", "of", "detri-", "mental", "cell–cell", "signals.", "Drugs", "that", "inhibit", "this", "tissue", "relocation", "by", "preventing", "mast", "cell", "migration", "may", "prove", "particularly", "effective", "in", "the", "treatment", "of", "mast", "cell-mediated", "disease.", "Human", "mast", "cells", "express", "the", "intermediate", "conductance", "Ca21-activated", "K1", "channel", "KCa3.1,", "which", "plays", "a", "critical", "role", "in", "their", "migration", "to", "diverse", "chemotactic", "stimuli", "[6],", "and", "to", "a", "lesser", "extent", "in", "their", "degranulation", "[7,", "8].", "Drugs", "that", "directly", "block", "this", "channel", "or", "which", "close", "it", "indirectly", "therefore", "have", "potential", "as", "novel", "therapies", "for", "mast", "cell-dependent", "disease.", "KCa3.1", "in", "human", "&", "2008", "WILEY-VCH", "Verlag", "GmbH", "&", "Co.", "KGaA,", "Weinheim", "www.eji-journal.eu" ]

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[ "Doss", "et", "al.", "Journal", "of", "Cardiothoracic", "Surgery", "2011,", "6:136", "http://www.cardiothoracicsurgery.org/content/6/1/136", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Comparative", "evaluation", "of", "left", "ventricular", "mass", "regression", "after", "aortic", "valve", "replacement:", "a", "prospective", "randomized", "analysis", "Mirko", "Doss*,", "Jeffrey", "P", "Wood,", "Arndt", "H", "Kiessling", "and", "Anton", "Moritz", "Abstract", "Background:", "We", "assessed", "the", "hemodynamic", "performance", "of", "various", "prostheses", "and", "the", "clinical", "outcomes", "after", "aortic", "valve", "replacement,", "in", "different", "age", "groups.", "Methods:", "One-hundred-and-twenty", "patients", "with", "isolated", "aortic", "valve", "stenosis", "were", "included", "in", "this", "prospective", "randomized", "randomised", "trial", "and", "allocated", "in", "three", "age-groups", "to", "receive", "either", "pulmonary", "autograft", "(PA,", "n", "=", "20)", "or", "mechanical", "prosthesis", "(MP,", "Edwards", "Mira", "n", "=", "20)", "in", "group", "1", "(age", "<", "55", "years),", "either", "stentless", "bioprosthesis", "(CE", "Prima", "Plus", "n", "=", "20)", "or", "MP", "(Edwards", "Mira", "n", "=", "20)", "in", "group", "2", "(age", "55-75", "years)", "and", "either", "stentless", "(CE", "Prima", "Plus", "n", "=", "20)", "or", "stented", "bioprosthesis", "(CE", "Perimount", "n", "=", "20)", "in", "group", "3", "(age", ">", "75).", "Clinical", "outcomes", "and", "hemodynamic", "performance", "were", "evaluated", "at", "discharge,", "six", "months", "and", "one", "year.", "Results:", "In", "group", "1,", "patients", "with", "PA", "had", "significantly", "lower", "mean", "gradients", "than", "the", "MP", "(2.6", "vs.", "10.9", "mmHg,", "p", "=", "0.0005)", "with", "comparable", "left", "ventricular", "mass", "regression", "(LVMR).", "Morbidity", "included", "1", "stroke", "in", "the", "PA", "population", "and", "1", "gastrointestinal", "bleeding", "in", "the", "MP", "subgroup.", "In", "group", "2,", "mean", "gradients", "did", "not", "differ", "significantly", "between", "both", "populations", "(7.0", "vs.", "8.9", "mmHg,", "p", "=", "0.81).", "The", "rate", "of", "LVMR", "and", "EF", "were", "comparable", "at", "12", "months;", "each", "group", "with", "one", "mortality.", "Morbidity", "included", "1", "stroke", "and", "1", "gastrointestinal", "bleeding", "in", "the", "stentless", "and", "3", "bleeding", "complications", "in", "the", "MP", "group.", "In", "group", "3,", "mean", "gradients", "did", "not", "differ", "significantly", "(7.8", "vs", "6.5", "mmHg,", "p", "=", "0.06).", "Postoperative", "EF", "and", "LVMR", "were", "comparable.", "There", "were", "3", "deaths", "in", "the", "stented", "group", "and", "no", "mortality", "in", "the", "stentless", "group.", "Morbidity", "included", "1", "endocarditis", "and", "1", "stroke", "in", "the", "stentless", "compared", "to", "1", "endocarditis,", "1", "stroke", "and", "one", "pulmonary", "embolism", "in", "the", "stented", "group.", "Conclusions:", "Clinical", "outcomes", "justify", "valve", "replacement", "with", "either", "valve", "substitute", "in", "the", "respective", "age", "groups.", "The", "PA", "hemodynamically", "outperformed", "the", "MPs.", "Stentless", "valves", "however,", "did", "not", "demonstrate", "significantly", "superior", "hemodynamics", "or", "outcomes", "in", "comparison", "to", "stented", "bioprosthesis", "or", "MPs.", "Keywords:", "Left", "Ventricular", "Mass,", "Aortic", "Valve", "Replacement,", "Prospective", "randomized", "Analysis", "Background", "Aortic", "stenosis", "is", "the", "predominant", "lesion", "in", "the", "majority", "of", "patients", "presenting", "with", "clinically", "significant", "aortic", "valve", "disease.", "The", "only", "definitive", "treatment", "of", "critical", "aortic", "stenosis", "is", "aortic", "valve", "replacement", "(AVR).", "In", "deciding", "the", "choice", "of", "prosthesis", "in", "simple", "aortic", "valve", "replacement,", "most", "surgeons", "recommend", "a", "mechanical", "valve", "in", "the", "younger", "patients", "and", "a", "stented", "bioprosthesis", "in", "older", "individuals.", "Within", "the", "last", "*", "Correspondence:", "mirkodoss@aol.com", "Department", "of", "Thoracic", "and", "Cardiovascular", "Surgery,", "Johann", "Wolfgang", "Goethe", "University,", "Frankfurt", "am", "Main,", "Germany", "decade,", "pulmonary", "autografts", "and", "stentless", "bioprosthesis", "have", "been", "established", "as", "alternatives", "to", "mechanical", "valves", "and", "stented", "bioprosthesis,", "respectively.", "The", "pre-", "cise", "age", "at", "which", "one", "prosthesis", "is", "preferred", "over", "the", "other", "is", "a", "matter", "of", "controversy,", "but", "recent", "studies", "indi-", "cate", "that", "patients", "over", "the", "age", "of", "65", "years", "should", "receive", "a", "bioprosthesis", "(stented", "or", "stentless)", "and", "patients", "whose", "life", "expectancy", "is", "at", "least", "15", "years", "should", "receive", "a", "mechanical", "valve", "[1].", "The", "latter", "group", "of", "patients", "would", "alternatively", "be", "eligible", "for", "a", "pulmonary", "autograft.", "Stent-", "less", "valves", "with", "their", "unique", "design", "features,", "that", "allow", "laminar", "flow", "resulting", "in", "less", "stress", "on", "leaflets,", "promise", "©", "2011", "Doss", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Ilic", "and", "Forbes", "BMC", "Medical", "Education", "2010,", "10:58", "http://www.biomedcentral.com/1472-6920/10/58", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Undergraduate", "medical", "student", "perceptions", "and", "use", "of", "Evidence", "Based", "Medicine:", "A", "qualitative", "study", "Dragan", "Ilic*,", "Kristian", "Forbes", "Abstract", "Background:", "Many", "medical", "schools", "teach", "the", "principles", "of", "Evidence", "Based", "Medicine", "(EBM)", "as", "a", "subject", "within", "their", "medical", "curriculum.", "Few", "studies", "have", "explored", "the", "barriers", "and", "enablers", "that", "students", "experience", "when", "studying", "medicine", "and", "attempting", "to", "integrate", "EBM", "in", "their", "clinical", "experience.", "The", "aim", "of", "this", "study", "was", "to", "identify", "undergraduate", "medical", "student", "perceptions", "of", "EBM,", "including", "their", "current", "use", "of", "its", "principles", "as", "students", "and", "perceived", "future", "use", "as", "clinicians.", "Methods:", "Third", "year", "medical", "students", "were", "recruited", "via", "email", "to", "participate", "in", "focus", "group", "discussions.", "Four", "focus", "groups", "were", "conducted", "separately", "across", "four", "hospital", "sites.", "All", "focus", "groups", "were", "conducted", "by", "the", "same", "facilitator.", "All", "discussions", "were", "transcribed", "verbatim,", "and", "analysed", "independently", "by", "the", "two", "authors", "according", "to", "the", "principles", "of", "thematic", "analysis.", "Results:", "Focus", "group", "discussions", "were", "conducted", "with", "23", "third-year", "medical", "students,", "representing", "three", "metropolitan", "and", "one", "rural", "hospital", "sites.", "Five", "key", "themes", "emerged", "from", "the", "analysis", "of", "the", "transcripts:", "(1)", "Rationale", "and", "observed", "use", "of", "EBM", "in", "practice,", "(2)", "Current", "use", "of", "EBM", "as", "students,", "(3)", "Perceived", "use", "of", "EBM", "as", "future", "clinicians,", "(4)", "Barriers", "to", "practicing", "EBM,", "and", "(5)", "Enablers", "to", "facilitate", "the", "integration", "of", "EBM", "into", "clinical", "practice.", "Key", "facilitators", "for", "promoting", "EBM", "to", "students", "include", "competency", "in", "EBM,", "mentorship", "and", "application", "to", "clinical", "disciplines.", "Barriers", "to", "EBM", "implementation", "include", "lack", "of", "visible", "application", "by", "senior", "clinicians", "and", "constraints", "by", "poor", "resourcing.", "Conclusions:", "The", "principles", "and", "application", "of", "EBM", "is", "perceived", "by", "medical", "students", "to", "be", "important", "in", "both", "their", "current", "clinical", "training", "and", "perceived", "future", "work", "as", "clinicians.", "Future", "research", "is", "needed", "to", "identify", "how", "medical", "students", "incorporate", "EBM", "concepts", "into", "their", "clinical", "practice", "as", "they", "gain", "greater", "clinical", "exposure", "and", "competence.", "Background", "Evidence", "based", "medicine", "(EBM)", "was", "introduced", "as", "a", "method", "for", "assisting", "clinicians", "with", "obtaining", "informa-", "tion", "and", "synthesising", "its", "usefulness", "to", "aid", "clinical", "deci-", "sion", "making.", "Medical", "decision", "making", "is", "aided", "by", "the", "principles", "of", "EBM", "when", "the", "best", "available", "evidence", "is", "integrated", "with", "a", "clinician’s", "expertise", "and", "patient", "prefer-", "ences,[1]", "regardless", "of", "whether", "the", "question", "is", "one", "of", "therapy,", "diagnosis,", "harm", "or", "prognosis.", "Elements", "of", "evi-", "dence", "based", "learning", "and", "practice", "include", "(i)", "asking", "an", "answerable", "question,", "(ii)", "systematically", "searching", "for", "and", "*", "Correspondence:", "dragan.ilic@med.monash.edu.au", "Monash", "Institute", "of", "Health", "Services", "Research,", "School", "of", "Public", "Health", "&", "Preventive", "Medicine,", "Monash", "University,", "Australia", "accessing", "evidence,", "(iii)", "critically", "appraising", "the", "evidence", "for", "quality,", "reliability", "and", "robustness,", "and", "(iv)", "integrating", "useful", "information", "into", "the", "clinical", "setting[2].", "Many", "medical", "schools", "are", "teaching", "EBM", "as", "a", "core", "requirement", "in", "their", "medical", "curriculum", "[3].", "The", "last", "dec-", "ade", "has", "seen", "the", "integration", "of", "EBM", "into", "the", "curriculum", "of", "medical", "courses,", "in", "both", "the", "undergraduate", "and", "post-", "graduate", "setting,", "as", "well", "as", "during", "pre-clinical", "and", "clinical", "years[4-9].", "Teaching", "the", "principles", "of", "EBM", "to", "medical", "stu-", "dents", "increases", "knowledge,", "improves", "critical", "appraisal", "skills", "and", "attitudes", "in", "both", "the", "undergraduate", "and", "post-", "graduate", "setting[4-9].", "Additionally,", "EBM", "content", "can", "be", "delivered", "as", "a", "standalone", "course,", "or", "integrated", "into", "exist-", "ing", "activities", "within", "the", "medical", "curriculum[2].", "©", "2010", "Ilic", "and", "Forbes;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Clinical", "research", "Cyclosporine", "A", "–", "treated", "nephrotic", "children", "show", "impaired", "vasodilatation", "but", "no", "autonomic", "neuropathy", "Aneta", "Czupryniak1,", "Anna", "Kałużyńska1,", "Anna", "Półtorak-Krawczyk1,", "Bartosz", "Ostrowski2,", "Bogusław", "Więcek2,", "Marcin", "Tkaczyk1", "1Division", "of", "Nephrology,", "Polish", "Mother’s", "Memorial", "Hospital", "Research", "Institute", "of", "Lodz,", "Poland", "2Institute", "of", "Electronics,", "Technical", "University", "of", "Lodz,", "Poland", "Submitted:", "14", "April", "2009", "Accepted:", "22", "February", "2010", "Arch", "Med", "Sci", "2010;", "6,", "4:", "573-577", "DOI:", "10.5114/aoms.2010.14470", "Copyright", "©", "2010", "Termedia", "&", "Banach", "A", "b", "s", "t", "r", "a", "c", "t", "Introduction:", "The", "aim", "of", "the", "study", "was", "to", "determine", "the", "effect", "of", "long-term", "cyclosporine", "A", "(CsA)", "treatment", "in", "children", "with", "idiopathic", "nephrotic", "syndrome", "on", "autonomic", "nerve", "function", "and", "peripheral", "blood", "flow", "assessed", "with", "thermography.", "Material", "and", "methods:", "The", "study", "group", "consisted", "of", "19", "nephrotic", "children", "treated", "with", "cyclosporine", "A", "compared", "to", "16", "healthy", "children.", "The", "assessment", "of", "blood", "flow", "was", "made", "based", "on", "the", "results", "of", "thermographic", "measurements", "during", "the", "cold", "stress", "test", "by", "an", "infrared", "radiation", "registering", "camera.", "Ewing’s", "battery", "of", "non-invasive", "tests", "was", "used", "to", "assess", "autonomic", "function.", "Results:", "The", "study", "showed", "diminished", "temperature", "increase", "after", "the", "cooling", "test", "in", "children", "with", "nephrotic", "syndrome", "treated", "with", "CsA.", "Sympathetic", "activity", "test", "results", "were", "comparable", "to", "healthy", "children.", "Conclusions:", "It", "may", "be", "hypothesized", "that", "cyclosporine", "A", "administered", "even", "in", "low", "doses", "induces", "small", "vessel", "dysfunction", "measured", "by", "the", "thermographic", "method.", "This", "effect", "seems", "to", "be", "independent", "of", "sympathetic", "nervous", "system", "involvement,", "which", "was", "absent", "in", "cyclosporine", "A", "treated", "nephrotic", "children.", "Key", "words:", "cyclosporine", "A,", "autonomic", "function,", "vasodilatation,", "thermography,", "children,", "nephrotic", "syndrome.", "Introduction", "Cyclosporine", "A", "(CsA)", "is", "used", "routinely", "in", "the", "immunosuppressive", "regimen", "in", "children", "with", "both", "steroid-dependent", "and", "steroid-resistant", "nephrotic", "syndrome", "(SD-NS", "and", "SR-NS)", "[1-3].", "However,", "its", "use", "is", "limited", "by", "adverse", "reactions,", "which", "include", "acute", "and", "chronic", "nephrotoxicity", "and", "hypertension", "[4,", "5].", "Mechanisms", "by", "which", "CsA", "treatment", "leads", "to", "nephrotoxicity", "and", "hypertension", "are", "poorly", "understood.", "It", "has", "been", "shown", "that", "acute", "dose-", "dependent", "CsA", "nephrotoxicity", "results", "from", "functional", "vasoconstriction", "of", "the", "afferent", "pre-glomerular", "arterioles", "followed", "by", "a", "decrease", "in", "renal", "blood", "flow", "[6].", "Prolonged", "vasoconstriction", "causing", "chronic", "ischaemia", "may", "contribute", "to", "chronic", "CsA-dependent", "tubulointerstitial", "changes", "[4,", "5,", "7,", "8].", "The", "concept", "of", "CsA", "inducing", "hypertension", "through", "impairment", "of", "vascular", "regulatory", "mechanisms", "is", "still", "under", "debate.", "Acute", "CsA-dependent", "impairment", "of", "peripheral", "blood", "flow", "presenting", "as", "Raynaud’s", "phenomenon", "(RP)", "has", "recently", "been", "described", "by", "Arinsoy", "et", "al.", "and", "Sharma", "et", "al.", "[9,", "10].", "Raynaud’s", "phenomenon", "is", "a", "symptom", "of", "Corresponding", "author:", "Marcin", "Tkaczyk,", "MD", "PhD", "Division", "of", "Nephrology", "Department", "of", "Paediatrics", "and", "Immunology", "Polish", "Mother’s", "Memorial", "Hospital", "Research", "Institute", "281/289", "Rzgowska", "St.", "93-338", "Lodz,", "Poland", "Phone:", "+48", "42", "271", "21", "40", "Fax:", "+48", "42", "271", "10", "91", "E-mail:", "mtkaczyk@uni.lodz.pl" ]

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[ "Bernard", "et", "al.", "BMC", "Gastroenterology", "2010,", "10:77", "http://www.biomedcentral.com/1471-230X/10/77", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "Hypoglycaemia", "following", "upper", "gastrointestinal", "surgery:", "case", "report", "and", "review", "of", "the", "literature", "Brandon", "Bernard1,", "Gregory", "A", "Kline1*,", "F", "John", "Service2", "Abstract", "Background:", "Hyperinsulinemic", "hypoglycemia", "is", "relatively", "recently", "recognized", "in", "persons", "undergoing", "bariatric", "surgery", "although", "knowledge", "and", "experience", "with", "this", "condition", "may", "not", "be", "commensurate", "with", "the", "number", "of", "such", "procedures", "being", "performed", "globally.", "This", "paper", "presents", "a", "novel", "case", "as", "an", "example", "of", "how", "such", "patients", "may", "present", "and", "how", "they", "may", "be", "investigated.", "Case", "Presentation:", "A", "69-year-old", "man", "was", "assessed", "3", "months", "post-fundoplication", "surgery", "for", "postprandial", "hypoglycaemia", "with", "neuroglycopenia", "that", "became", "progressively", "severe.", "A", "72-h", "fast", "failed", "to", "show", "hypoglycaemia.", "During", "a", "clinic", "visit,", "the", "patient", "became", "confused", "and", "had", "a", "low", "plasma", "glucose,", "high", "plasma", "insulin,", "and", "high", "plasma", "C-peptide;", "symptoms", "were", "relieved", "with", "glucose.", "No", "tumours", "were", "visualized", "on", "CT,", "MRI,", "or", "endoscopic", "ultrasound.", "A", "total", "body", "Indium111-octreotide", "scan", "was", "negative.", "Selective", "arterial", "calcium", "stimulation", "showed", "a", "high", "insulin", "gradient", "in", "the", "splenic", "and", "superior", "mesenteric", "arteries,", "suggesting", "diffuse", "pancreatic", "beta", "cell", "hyperplasia.", "The", "patient", "declined", "pancreatic", "resection", "and", "recurrent", "symptomatic", "hypoglycaemia", "was", "successfully", "prevented", "with", "low", "dose", "octreotide.", "Conclusions:", "Although", "increasingly", "recognized", "following", "bariatric", "surgery,", "this", "is", "the", "first", "reported", "development", "of", "NIPHS", "(non-insulinoma", "pancreatogenous", "hypoglycemia", "syndrome)", "following", "fundoplication", "surgery,", "as", "well", "as", "the", "first", "documented", "use", "of", "octreotide", "in", "post-operative", "NIPHS.", "Medical", "management", "may", "be", "an", "alternative", "to", "surgery", "for", "patients", "with", "this", "rare", "condition.", "Background", "It", "is", "common", "to", "see", "patients", "presenting", "with", "symptoms", "attributed", "to", "“hypoglycaemia”", "in", "endocrinology", "and", "gen-", "eral", "medicine", "clinics.", "The", "first", "step", "in", "evaluation", "requires", "documentation", "that", "hypoglycaemia", "is", "in", "fact", "present", "and", "the", "cause", "of", "the", "symptoms.", "Once", "hypoglycaemia", "is", "pro-", "ven,", "the", "next", "step", "is", "to", "determine", "whether", "it", "is", "mediated", "by", "insulin", "or", "by", "an", "alternate", "disease", "process.", "Most", "insulin-", "mediated", "hypoglycaemia", "is", "due", "to", "either", "exogenous", "insulin", "use", "or", "the", "presence", "of", "an", "insulinoma", "but", "in", "recent", "years,", "the", "differential", "diagnosis", "has", "expanded", "to", "include", "other", "forms", "of", "beta", "cell", "dysfunction,", "some", "of", "which", "may", "simu-", "late", "insulinoma,", "as", "illustrated", "in", "the", "following", "case.", "Case", "presentation", "A", "69-year-old", "non-obese", "man", "(BMI", "25.2", "kg/m2)", "pre-", "sented", "with", "a", "3", "month", "history", "of", "progressive", "symptoms", "*", "Correspondence:", "gakline@ucalgary.ca", "1Division", "of", "Endocrinology,", "Faculty", "of", "Medicine,", "University", "of", "Calgary,", "Calgary,", "Alberta", "Canada", "of", "hypoglycaemia", "following", "meals.", "He", "noted", "that", "symp-", "toms", "first", "appeared", "14", "years", "ago", "at", "which", "time", "a", "formal", "72", "hour", "fast", "failed", "to", "show", "any", "hypoglycaemia.", "How-", "ever,", "his", "symptoms", "had", "become", "dramatically", "worse", "2", "months", "after", "undergoing", "a", "recent", "Nissan", "fundoplication", "surgery", "to", "repair", "a", "paraesophageal", "hiatus", "hernia.", "The", "episodes", "were", "characterized", "by", "agitation,", "sweatiness,", "rapid", "heart", "rate,", "tremor,", "light", "headedness,", "confusion", "and", "cognitive", "changes", "likened", "to", "alcohol", "intoxication", "that", "occurred", "an", "hour", "or", "two", "after", "meals.", "One", "such", "episode", "had", "resulted", "in", "loss", "of", "consciousness", "and", "subsequent", "involvement", "in", "a", "motor", "vehicle", "crash.", "There", "were", "no", "nocturnal", "symptoms", "and", "no", "history", "of", "weight", "loss,", "abdominal", "pain", "or", "diarrhoea.", "He", "denied", "the", "use", "of", "oral", "hypoglycaemic", "agents", "or", "insulin.", "Initial", "investigations", "were", "performed", "during", "his", "first", "clinical", "visit", "when", "the", "patient", "was", "noticed", "to", "become", "diaphoretic", "and", "confused", "during", "the", "history", "and", "physi-", "cal", "examination.", "The", "onset", "of", "these", "symptoms", "occurred", "at", "approximately", "1.5", "hours", "after", "breakfast.", "Plasma", "©", "2010", "Bernard", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "CLINICS", "2011;66(2):359-361", "CASE", "REPORT", "DOI:10.1590/S1807-59322011000200030", "Metanephric", "Adenoma:", "clinical,", "imaging,", "and", "Histological", "findings", "Fa´", "bio", "Ce´", "sar", "Miranda", "Torricelli,I", "Giovanni", "Scala", "Marchini,I", "Rodrigo", "Sousa", "Madeira", "Campos,II", "Antoˆ", "nio", "Otero", "GilIII", "I", "Urologic", "Surgeon,", "Urology", "Department,", "Faculdade", "de", "Medicina", "da", "Universidade", "de", "Sao,", "Sao", "Paulo", "-", "SP", "–", "Brazil.", "II", "Urologic", "Surgeon,", "Urology", "Department,", "Hospital", "do", "Servidor", "Pu´", "blico", "Estadual,", "Sao", "Paulo", "-", "SP", "–", "Brasil.", "III", "Urology", "-", "Instituto", "Dante", "Pazanezzi,", "Sao", "Paulo,", "S", "a˜o", "Paulo,", "Brazil.", "Email:", "fabio_torri@yahoo.com.br", "Tel.:", "55", "11", "5533-4900", "INTRODUCTION", "Metanephric", "adenoma", "(MA),", "also", "designated", "nephrono-", "genic", "nephroma", "or", "renal", "epithelial", "tumor", "resembling", "immature", "nephron,", "has", "just", "been", "recently", "recognized", "as", "a", "special", "type", "of", "benign", "renal", "epithelial", "tumor.", "Only", "few", "reports", "are", "found", "in", "the", "literature", "regarding", "this", "rare", "renal", "tumor.", "The", "purpose", "of", "this", "paper", "is", "to", "describe", "our", "clinical,", "imaging", "and", "histological", "/", "immunohistochemical", "observa-", "tions", "of", "MA", "diagnosed", "in", "two", "patients", "and", "compare", "these", "data", "to", "previous", "information", "reported", "in", "medical", "databases.", "CASE", "REPORT", "The", "first", "case", "refers", "to", "a", "70-years-old", "female", "patient,", "who", "except", "by", "systemic", "arterial", "hypertension", "was", "completely", "healthy.", "During", "routine", "examinations,", "a", "mass", "of", "4.5", "cm", "located", "on", "the", "lower", "third", "of", "her", "right", "kidney", "was", "incidentally", "found.", "At", "that", "time,", "the", "patient", "presented", "only", "low-grade", "fever", "and", "weakness", "for", "about", "two", "weeks.", "Abdominal", "ultrassonography", "(USG)", "showed", "hypoechoec", "mass", "with", "solid", "aspect", "and", "irregular", "limits.", "It", "was", "heterogeneous", "and", "exofitic,", "containing", "septation", "and", "cystic", "areas", "in", "its", "interior.", "Magnetic", "resonance", "imaging", "(MRI)", "showed", "a", "solid", "mass", "5.2", "cm", "for", "its", "higher", "dimension", "located", "in", "right", "kidney", "with", "same", "hemorrhagic", "foci", "and", "no", "sign", "of", "peri-renal", "invasion", "(Figure", "1).", "Also,", "simple", "renal", "cysts", "were", "evidenced.", "The", "patient", "was", "submitted", "to", "a", "successful", "partial", "nephrectomy", "by", "open", "surgery,", "evolving", "uneventfully.", "Pathologic", "examination", "of", "surgical", "specimen", "revealed", "a", "firm", "lesion", "of", "light", "brown", "tissue", "with", "reticulated", "central", "area", "and", "clear", "delimitation", "from", "the", "adjacent", "parenchyma.", "Microscopic", "evaluation", "showed", "no", "cellular", "atypical", "or", "mitotic", "activity.", "Peri-renal", "adipose", "tissue", "was", "free", "from", "neoplasic", "invasion.", "The", "second", "patient", "was", "a", "23-year-old", "man", "with", "no", "previous", "heath", "problem,", "who", "presented", "with", "flank", "pain", "for", "one", "month.", "Abdominal", "USG", "showed", "a", "464", "cm", "nodular,", "solid", "and", "heterogenic", "lesion", "with", "hyperecogenic", "areas", "and", "exofitic", "characteristics", "in", "the", "lower", "third", "of", "right", "renal", "parenchyma.", "Computed", "tomography", "(CT)", "confirmed", "the", "presence", "of", "a", "4", "cm", "expansive", "tumoral", "formation", "with", "Copyright", "2011", "CLINICS", "–", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://", "creativecommons.org/licenses/by-nc/3.0/)", "which", "permits", "unrestricted", "non-", "commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "intermediate", "attenuation", "and", "minimum", "venous", "contrast", "enhancing", "at", "that", "anatomic", "site", "(Figure", "2).", "Partial", "nephrect-", "omy", "was", "again", "the", "therapeutic", "choice.", "The", "patient", "evolved", "well", "but", "an", "arterial-venous", "fistula", "clinically", "manifested", "by", "hematuria", "was", "diagnosed", "in", "post-operative", "(PO)", "day", "five.", "The", "fistula", "was", "successfully", "embolized", "by", "arteriography", "and", "no", "other", "complications", "occurred.", "Immunohistochemical", "study", "employing", "incubation", "of", "histological", "cuts", "with", "mono", "and", "polyclonal", "antibodies", "(panels)", "showed", "a", "profile", "focally", "and", "positive", "to", "WT-1,", "EMA", "and", "CK7.", "Both", "patients", "are", "free", "of", "neoplasic", "disease", "with", "no", "signs", "of", "recurrence", "after", "2", "years", "of", "follow", "up.", "DISCUSSION", "MA", "is", "a", "renal", "tumor", "with", "benign", "behavior.", "The", "classification", "is", "based", "on", "a", "combination", "of", "histological,", "immunohistochemical,", "and", "genetic", "features.", "Most", "small", "MA", "tumors", "are", "well", "circumscribed,", "firm,", "and", "white;", "larger", "tumors", "may", "be", "hemorrhagic", "and", "softer.", "The", "cytology", "of", "a", "few", "cases", "has", "been", "described1", "and", "is", "composed", "of", "tight,", "short", "papillae", "and", "loose", "sheets", "of", "cells", "with", "scant", "cytoplasm,", "round", "nuclei,", "fine", "chromatin", "and", "rare", "small", "nucleoli.", "By", "analyzing", "all", "described", "findings", "at", "immunohistochemical", "and", "lectin", "histochemical", "studies,", "MA", "has", "shown", "reactivity", "for", "keratin", "(CK7", "is", "the", "most", "common),", "CD", "57,", "vimentin,", "S-100", "protein,", "EMA,", "lysozyme,", "359", "Figure", "1", "-", "MRI", "-", "solid", "mass", "5.2", "cm", "in", "higher", "dimension", "located", "in", "right", "kidney", "with", "same", "hemorrhagic", "foci", "and", "no", "sign", "of", "perirenal", "invasion" ]

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[ "BMC", "Health", "Services", "Research", "BioMed", "Central", "Research", "article", "Open", "Access", "Record", "linkage", "research", "and", "informed", "consent:", "who", "consents?", "Nicole", "Huang1,", "Shu-Fang", "Shih2,", "Hsing-Yi", "Chang2", "and", "Yiing-Jenq", "Chou*1", "Address:", "1Institute", "of", "Public", "Health,", "School", "of", "Medicine,", "National", "Yang-Ming", "University,", "No.", "155,", "Section", "2,", "Li-Nong", "Street,", "Taipei", "112,", "Taiwan,", "R.O.C", "and", "2Center", "for", "Health", "Policy", "Research", "and", "Development,", "National", "Health", "Research", "Institutes,", "No.", "35,", "Keyan", "Road,", "Zhunan", "Town,", "Miaoli", "County", "350,", "Taiwan,", "R.O.C", "Email:", "Nicole", "Huang", "-", "syhuang@ym.edu.tw;", "Shu-Fang", "Shih", "-", "annsshih@nhri.org.tw;", "Hsing-Yi", "Chang", "-", "hsingyi@nhri.org.tw;", "Yiing-", "Jenq", "Chou*", "-", "yjchou@ym.edu.tw", "*", "Corresponding", "author", "Published:", "12", "February", "2007", "BMC", "Health", "Services", "Research", "2007,", "7:18", "doi:10.1186/1472-6963-7-18", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1472-6963/7/18", "Received:", "24", "August", "2006", "Accepted:", "12", "February", "2007", "©", "2007", "Huang", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Linking", "computerized", "health", "insurance", "records", "with", "routinely", "collected", "survey", "data", "is", "becoming", "increasingly", "popular", "in", "health", "services", "research.", "However,", "if", "consent", "is", "not", "universal,", "the", "requirement", "of", "written", "informed", "consent", "may", "introduce", "a", "number", "of", "research", "biases.", "The", "participants", "of", "a", "national", "health", "survey", "in", "Taiwan", "were", "asked", "to", "have", "their", "questionnaire", "results", "linked", "to", "their", "national", "health", "insurance", "records.", "This", "study", "compares", "those", "who", "consented", "with", "those", "who", "refused.", "Methods:", "A", "national", "representative", "sample", "(n", "=", "14,611", "adults)", "of", "the", "general", "adult", "population", "aged", "20", "years", "or", "older", "who", "participated", "in", "the", "Taiwan", "National", "Health", "Interview", "Survey", "(NHIS)", "and", "who", "provided", "complete", "survey", "information", "were", "used", "in", "this", "study.", "At", "the", "end", "of", "the", "survey,", "the", "respondents", "were", "asked", "if", "they", "would", "give", "permission", "to", "access", "their", "National", "Health", "Insurance", "records.", "Information", "given", "by", "the", "interviewees", "in", "the", "survey", "was", "used", "to", "analyze", "who", "was", "more", "likely", "to", "consent", "to", "linkage", "and", "who", "wasn't.", "Results:", "Of", "the", "14,611", "NHIS", "participants,", "12,911", "(88%)", "gave", "consent,", "and", "1,700", "(12%)", "denied", "consent.", "The", "elderly,", "the", "illiterate,", "those", "with", "a", "lower", "income,", "and", "the", "suburban", "area", "residents", "were", "significantly", "more", "likely", "to", "deny", "consent.", "The", "aborigines", "were", "significantly", "less", "likely", "to", "refuse.", "No", "discrepancy", "in", "gender", "and", "self-reported", "health", "was", "found", "between", "individuals", "who", "consented", "and", "those", "who", "refused.", "Conclusion:", "This", "study", "is", "the", "first", "population-based", "study", "in", "assessing", "the", "consent", "pattern", "in", "a", "general", "Asian", "population.", "Consistent", "with", "people", "in", "Western", "societies,", "in", "Taiwan,", "a", "typical", "Asian", "society,", "a", "high", "percentage", "of", "adults", "gave", "consent", "for", "their", "health", "insurance", "records", "and", "questionnaire", "results", "to", "be", "linked.", "Consenters", "differed", "significantly", "from", "non-consenters", "in", "important", "aspects", "such", "as", "age,", "ethnicity,", "and", "educational", "background.", "Consequently,", "having", "a", "high", "consent", "rate", "(88%)", "may", "not", "fully", "eliminate", "the", "possibility", "of", "selection", "bias.", "Researchers", "should", "take", "this", "source", "of", "bias", "into", "consideration", "in", "their", "study", "design", "and", "investigate", "any", "potential", "impact", "of", "this", "source", "of", "bias", "on", "their", "results.", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Evolutionary", "Applications", "ISSN", "1752-4571", "O", "R", "I", "G", "I", "N", "A", "L", "A", "R", "T", "I", "C", "L", "E", "Turner", "syndrome", "and", "the", "evolution", "of", "human", "sexual", "dimorphism", "Bernard", "Crespi", "Department", "of", "Biosciences,", "Simon", "Fraser", "University,", "Burnaby,", "BC,", "Canada", "Keywords", "genomic", "imprinting,", "sexual", "dimorphism,", "Turner", "syndrome,", "X", "chromosome.", "Correspondence", "Bernard", "Crespi,", "Killam", "Research", "Professor,", "Department", "of", "Biosciences,", "Simon", "Fraser", "University,", "Burnaby,", "BC", "V5A", "1S6,", "Canada.", "Tel.:", "778", "782", "3533;", "fax:", "778", "782", "3496;", "e-mail:", "crespi@sfu.ca", "Received:", "19", "November", "2007", "Accepted:", "17", "January", "2008", "First", "published", "online:", "22", "February", "2008", "doi:10.1111/j.1752-4571.2008.00017.x", "Abstract", "Turner", "syndrome", "is", "caused", "by", "loss", "of", "all", "or", "part", "of", "an", "X", "chromosome", "in", "females.", "A", "series", "of", "recent", "studies", "has", "characterized", "phenotypic", "differences", "between", "Turner", "females", "retaining", "the", "intact", "maternally", "inherited", "versus", "pater-", "nally", "inherited", "X", "chromosome,", "which", "have", "been", "interpreted", "as", "evidence", "for", "effects", "of", "X-linked", "imprinted", "genes.", "In", "this", "study", "I", "demonstrate", "that", "the", "differ-", "ences", "between", "Turner", "females", "with", "a", "maternal", "X", "and", "a", "paternal", "X", "broadly", "parallel", "the", "differences", "between", "males", "and", "normal", "females", "for", "a", "large", "suite", "of", "traits,", "including", "lipid", "profile", "and", "visceral", "fat,", "response", "to", "growth", "hormone,", "sensorineural", "hearing", "loss,", "congenital", "heart", "and", "kidney", "malformations,", "neuro-", "anatomy", "(sizes", "of", "the", "cerebellum,", "hippocampus,", "caudate", "nuclei", "and", "superior", "temporal", "gyrus),", "and", "aspects", "of", "cognition.", "This", "pattern", "indicates", "that", "diverse", "aspects", "of", "human", "sex", "differences", "are", "mediated", "in", "part", "by", "X-linked", "genes,", "via", "genomic", "imprinting", "of", "such", "genes,", "higher", "rates", "of", "mosaicism", "in", "Turner", "females", "with", "an", "intact", "X", "chromosome", "of", "paternal", "origin,", "karyotypic", "differences", "between", "Turner", "females", "with", "a", "maternal", "versus", "paternal", "X", "chromosome,", "or", "some", "combination", "of", "these", "phenomena.", "Determining", "the", "relative", "contributions", "of", "genomic", "imprinting,", "karyotype", "and", "mosaicism", "to", "variation", "in", "Turner", "syn-", "drome", "phenotypes", "has", "important", "implications", "for", "both", "clinical", "treatment", "of", "individuals", "with", "this", "syndrome,", "and", "hypotheses", "for", "the", "evolution", "and", "develop-", "ment", "of", "human", "sexual", "dimorphism.", "Introduction", "Genomic", "syndromes", "are", "alterations", "to", "a", "suite", "of", "contigu-", "ous", "genes,", "such", "as", "deletions,", "duplications,", "or", "aneuploi-", "dies,", "that", "result", "in", "characteristic", "sets", "of", "phenotypic", "changes,", "some", "of", "which", "may", "require", "medical", "interven-", "tions", "(e.g.", "Feinstein", "and", "Singh", "2007).", "Such", "syndromes", "provide", "unique", "insights", "into", "human", "evolution", "because", "they", "represent", "naturally", "occurring", "genomic", "variation", "that", "can", "be", "linked", "with", "specific", "phenotypic", "consequences", "for", "human", "growth,", "development", "and", "cognition.", "For", "example,", "Haig", "and", "Wharton", "(2003),", "Oliver", "et", "al.", "(2007)", "and", "Crespi", "and", "Badcock", "(2008)", "show", "how", "the", "phenotypes", "of", "Prader-", "Willi", "and", "Angelman", "syndromes,", "which", "are", "due", "to", "diamet-", "ric", "alterations", "of", "a", "region", "of", "chromosome", "15", "bearing", "a", "cluster", "of", "imprinted", "genes,", "provide", "insight", "into", "the", "evolu-", "tion", "of", "human", "childhood", "and", "mother–offspring", "interac-", "ª", "2008", "The", "Author", "Journal", "compilation", "ª", "2008", "Blackwell", "Publishing", "Ltd", "1", "(2008)", "449–461", "tions", "mediated", "by", "imprinting", "effects.", "Similarly,", "Williams", "syndrome,", "caused", "by", "deletions", "of", "a", "region", "of", "chromo-", "some", "7,", "involves", "an", "unusual", "cognitive", "profile", "of", "spared", "or", "enhanced", "expressive-language", "skills,", "but", "greatly", "impaired", "visual-spatial", "abilities,", "which", "has", "been", "interpreted", "as", "pro-", "viding", "insights", "into", "the", "genetic", "and", "neurological", "architec-", "ture", "of", "human", "language", "(Tassabehji", "2003;", "Meyer-", "Lindenberg", "et", "al.", "2006;", "Brock", "2007).", "Duplications", "of", "the", "Williams-syndrome", "region,", "by", "contrast,", "involve", "high", "rates", "of", "autism,", "with", "expressive", "language", "abilities", "selectively", "impaired", "(Berg", "et", "al.", "2007).", "Several", "genomic", "syndromes", "involve", "gains", "or", "loss", "of", "entire", "chromosomes.", "Loss", "of", "part", "or", "all", "of", "an", "X", "chromo-", "some", "causes", "Turner", "syndrome", "in", "females,", "whereas", "gains", "of", "one", "or", "more", "X", "chromosomes", "result", "in", "Klinefelter", "syn-", "drome", "in", "males", "(Simpson", "et", "al.", "2003;", "Bondy", "2006).", "These", "syndromes", "are", "of", "particular", "interest", "in", "human", "evolution", "449" ]

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[ "Intensive", "Care", "Med", "(2011)", "37:1143–1150", "DOI", "10.1007/s00134-011-2253-x", "O", "R", "I", "G", "I", "N", "A", "L", "Ranveig", "Lind", "Geir", "F.", "Lorem", "Per", "Nortvedt", "Olav", "Hevrøy", "Family", "members’", "experiences", "of", "‘‘wait", "and", "see’’", "as", "a", "communication", "strategy", "in", "end-of-life", "decisions", "Received:", "24", "August", "2010", "Accepted:", "1", "April", "2011", "Published", "online:", "28", "May", "2011", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Electronic", "supplementary", "material", "The", "online", "version", "of", "this", "article", "(doi:10.1007/s00134-011-2253-x)", "contains", "supplementary", "material,", "which", "is", "available", "to", "authorized", "users.", "R.", "Lind", "())", "Intensive", "Care", "Unit,", "University", "Hospital", "of", "Northern", "Norway,", "Opin-klin,", "Pb", "6060,", "9038", "Tromsø,", "Norway", "e-mail:", "Ranveig.Lind@unn.no", "Tel.:", "?47-91184108", "Fax:", "?47-77626192", "R.", "Lind", "G.", "F.", "Lorem", "Department", "of", "Care", "and", "Health", "Sciences,", "University", "of", "Tromsø,", "Tromsø,", "Norway", "G.", "F.", "Lorem", "e-mail:", "geir.lorem@uit.no", "Tel.:", "?47-77646533", "P.", "Nortvedt", "Section", "for", "Medical", "Ethics,", "University", "of", "Oslo,", "Oslo,", "Norway", "e-mail:", "p.nortvedt@medisin.uio.no", "O.", "Hevrøy", "be", "unclear,", "and", "few", "study", "participants", "Intensive", "Care", "Unit,", "Haukeland", "University", "experienced", "shared", "decision-making.", "Hospital,", "Bergen,", "Norway", "The", "clinician’s", "expression", "‘‘wait", "and", "e-mail:", "olav.hevroy@helse-bergen.no", "see’’", "hides", "and", "delays", "the", "communi-", "cation", "of", "honest", "and", "clear", "Abstract", "Purpose:", "The", "aim", "of", "information.", "When", "physicians", "finally", "this", "study", "is", "to", "examine", "family", "address", 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"their", "role", "to", "Introduction", "involving", "serious", "interventions", "should", "be", "based", "on", "informed", "consent", "[2].", "However,", "ICU", "patients", "generally", "Most", "deaths", "in", "intensive", "care", "units", "(ICUs)", "take", "place", "after", "have", "impaired", "cognition", "and", "are", "unable", "to", "decide", "for", "a", "decision", "is", "made", "to", "limit", "or", "withdraw", "medical", "treatment.", "themselves;", "therefore,", "they", "depend", "on", "surrogates", "to", "make", "Questions", "regarding", "the", "level", "and", "aim", "of", "treatment", "form", "decisions", "on", "their", "behalf", "[3].", "Traditionally,", "and", "due", "to", "an", "important", "part", "of", "day-to-day", "activities", "in", "ICUs", "[1].", "legislation,", "families", "in", "European", "countries", "have", "been", "less", "According", "to", "Norwegian", "legislation,", "healthcare", "decisions", "involved", "in", "end-of-life", "decisions", "than", "in", "the", 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[ "www.jkns.or.kr", "http://dx.doi.org/10.3340/jkns.2012.52.4.346", "J", "Korean", "Neurosurg", "Soc", "52", ":", "346-352,", "2012", "Print", "ISSN", "2005-3711", "On-line", "ISSN", "1598-7876", "Copyright", "©", "2012", "The", "Korean", "Neurosurgical", "Society", "Clinical", "Article", "Comparison", "of", "Posterior", "Fixation", "Alone", "and", "Supplementation", "with", "Posterolateral", "Fusion", "in", "Thoracolumbar", "Burst", "Fractures", "Jong-Uk", "Hwang,", "M.D.,", "Jin-Woo", "Hur,", "M.D.,", "Jong-Won", "Lee,", "M.D.,", "Ki-Young", "Kwon,", "M.D.,", "Hyun-Koo", "Lee,", "M.D.,", "Ph.D.", "Department", "of", "Neurosurgery,", "Cheongju", "St.", "Mary’s", "Hospital,", "Cheongju,", "Korea", "Objective", ":", "We", "compared", "the", "radiological", "and", "clinical", "outcomes", "between", "patients", "who", "underwent", "posterior", "fixation", "alone", "and", "supplemented", "with", "fusion", "following", "the", "onset", "of", "thoracolumbar", "burst", "fractures.", "In", "addition,", "we", "also", "evaluated", "the", "necessity", "of", "posterolateral", "fusion", "for", "patients", "treated", "with", "posterior", "pedicle", "screw", "fixation.", "Methods", ":", "From", "January", "2007", "to", "December", "2009,", "46", "consecutive", "patients", "with", "thoracolumbar", "burst", "fracture", "were", "included", "in", "this", "study.", "On", "the", "basis", "of", "posterolateral", "fusion,", "we", "divided", "our", "patients", "into", "the", "non-fusion", "group", "and", "the", "fusion", "group.", "The", "radiological", "assessment", "was", "performed", "according", "to", "the", "Cobb’s", "method,", "and", "results", "were", "obtained", "at", "immediately,", "3,", "6,", "12", "months", "after", "surgery.", "The", "clinical", "outcomes", "were", "evaluated", "us-", "ing", "the", "modified", "Mcnab", "criteria", "at", "the", "final", "follow-up.", "Results", ":", "The", "demographic", "data", "and", "the", "mean", "follow-up", "period", "were", "similar", "between", "the", "two", "groups.", "Patients", "of", "both", "groups", "achieved", "satisfactory", "clinical", "outcomes.", "The", "mean", "loss", "of", "kyphosis", "correction", "showed", "that", "patients", "of", "both", "groups", "experienced", "loss", "of", "correction", "with", "no", "respect", "to", "whether", "they", "underwent", "the", "posterolateral", "fusion.", "There", "was", "no", "significant", "difference", "in", "the", "degree", "of", "loss", "of", "correction", "at", "any", "time", "points", "of", "the", "follow-up", "between", "the", "two", "groups.", "In", "addition,", "we", "also", "compared", "the", "effect", "of", "fixed", "levels", "(i.e.,", "short", "versus", "long", "segment)", "on", "loss", "of", "correction", "be-", "tween", "the", "two", "groups", "and", "there", "was", "no", "significant", "difference.", "There", "were", "no", "major", "complications", "postoperatively", "and", "during", "follow-up", "period.", "Conclusion", ":", "We", "suggest", "that", "posterolateral", "fusion", "may", "be", "unnecessary", "for", "patients", "with", "thoracolumbar", "burst", "fractures", "who", "underwent", "posterior", "pedicle", "screw", "fixation.", "Key", "Words", ":", "Thoracolumbar", "burst", "fracture", "·", "Posterior", "pedicle", "screw", "fixation", "·", "Posterolateral", "fusion", "·", "Loss", "of", "kyphosis", "correction.", "INTRODUCTION", "The", "thoracolumbar", "spine", "fracture", "is", "one", "of", "the", "fractures", "that", "are", "encountered", "the", "most", "frequently", "in", "a", "clinical", "settings,", "and", "it", "is", "involved", "in", "almost", "90%", "of", "all", "spinal", "injuries.", "In", "addition,", "10%", "to", "20%", "of", "them", "are", "burst", "fractures3,7,8).", "Some", "mechanical", "factors", "make", "the", "thoracolumbar", "spine", "susceptible", "to", "fracture", "following", "trauma.", "As", "a", "typical", "example,", "the", "thoracolumbar", "junction", "is", "a", "unique", "part", "of", "the", "spinal", "column", "where", "the", "spine", "undergoes", "the", "transition", "from", "the", "rigid", "kyphotic", "thoracic", "to", "mobile", "lordotic", "lumbar", "spine.", "This", "transitional", "anatomy", "renders", "it", "vulnerable", "to", "the", "trauma", "from", "a", "fall", "or", "a", "motor", "vehicle", "accident17,18,36).", "Thora-", "columbar", "burst", "fractures", "usually", "occur", "due", "to", "a", "substantial", "axial", "loading", "force,", "which", "results", "in", "a", "compression", "failure", "of", "the", "ante-", "rior", "and", "middle", "spinal", "columns.", "There", "are", "some", "characteristic", "findings", "in", "the", "burst", "fractures;", "comminution", "of", "the", "injured", "ver-", "tebral", "body,", "progressive", "kyphotic", "deformity", "of", "the", "sagittal", "align-", "ment,", "and", "canal", "compromise", "caused", "by", "retropulsion", "of", "the", "frac-", "ture", "segment,", "which", "may", "produce", "neurological", "deficits.", "The", "management", "of", "thoracolumbar", "burst", "fractures", "still", "re-", "mains", "a", "challenging", "issue.", "Treatment", "varies", "ranging", "from", "the", "conservative", "management", "to", "various", "types", "of", "surgery.", "In", "addi-", "tion,", "there", "is", "a", "great", "variability", "in", "the", "indications", "depending", "on", "surgeons.", "Furthermore,", "diverse", "treatments", "have", "been", "proposed", "for", "thoracolumbar", "burst", "fractures", "by", "different", "authors35,38).", "To", "date,", "many", "published", "studies", "have", "reported", "this", "issue.", "It", "re-", "mains", "unclear,", "however,", "which", "treatment", "modalities", "would", "be", "more", "effective", "between", "the", "conservative", "and", "surgical", "manage-", "•", "Received", ":", "June", "13,", "2012", "•", "Revised", ":", "August", "28,", "2012", "•", "Accepted", ":", "October", "4,", "2012", "•", "Address", "for", "reprints", ":", "Jin-Woo", "Hur,", "M.D.", "Department", "of", "Neurosurgery,", "Cheongju", "St.", "Mary’s", "Hospital,", "173-19", "Juseong-ro,", "Sangdang-gu,", "Cheongju", "360-568,", "Korea", "Tel", ":", "+82-43-219-8467,", "Fax", ":", "+82-43-211-7925,", "E-mail", ":", "somalh@naver.com", "•", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "346" ]

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[ "Bilardi", "et", "al.", "BMC", "Public", "Health", "2010,", "10:70", "http://www.biomedcentral.com/1471-2458/10/70", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Incentive", "payments", "to", "general", "practitioners", "aimed", "at", "increasing", "opportunistic", "testing", "of", "young", "women", "for", "chlamydia:", "a", "pilot", "cluster", "randomised", "controlled", "trial", "Jade", "E", "Bilardi1*,", "Christopher", "K", "Fairley1,2,", "Meredith", "J", "Temple-Smith3,", "Marie", "V", "Pirotta3,", "Kathleen", "M", "McNamee4,", "Siobhan", "Bourke2,", "Lyle", "C", "Gurrin5,", "Margaret", "Hellard6,", "Lena", "A", "Sanci3,", "Michelle", "J", "Wills7,", "Jennifer", "Walker1,", "Marcus", "Y", "Chen1,2,", "Jane", "S", "Hocking8", "Abstract", "Background:", "Financial", "incentives", "have", "been", "used", "for", "many", "years", "internationally", "to", "improve", "quality", "of", "care", "in", "general", "practice.", "The", "aim", "of", "this", "pilot", "study", "was", "to", "determine", "if", "offering", "general", "practitioners", "(GP)", "a", "small", "incentive", "payment", "per", "test", "would", "increase", "chlamydia", "testing", "in", "women", "aged", "16", "to", "24", "years,", "attending", "general", "practice.", "Methods:", "General", "practice", "clinics", "(n", "=", "12)", "across", "Victoria,", "Australia,", "were", "cluster", "randomized", "to", "receive", "either", "a", "$AUD5", "payment", "per", "chlamydia", "test", "or", "no", "payment", "for", "testing", "16", "to", "24", "year", "old", "women", "for", "chlamydia.", "Data", "were", "collected", "on", "the", "number", "of", "chlamydia", "tests", "and", "patient", "consultations", "undertaken", "by", "each", "GP", "over", "two", "time", "periods:", "12", "month", "pre-trial", "and", "6", "month", "trial", "period.", "The", "impact", "of", "the", "intervention", "was", "assessed", "using", "a", "mixed", "effects", "logistic", "regression", "model,", "accommodating", "for", "clustering", "at", "GP", "level.", "Results:", "Testing", "increased", "from", "6.2%", "(95%", "CI:", "4.2,", "8.4)", "to", "8.8%", "(95%", "CI:", "4.8,", "13.0)", "(p", "=", "0.1)", "in", "the", "control", "group", "and", "from", "11.5%", "(95%", "CI:", "4.6,", "18.5)", "to", "13.4%", "(95%", "CI:", "9.5,", "17.5)", "(p", "=", "0.4)", "in", "the", "intervention", "group.", "Overall,", "the", "intervention", "did", "not", "result", "in", "a", "significant", "increase", "in", "chlamydia", "testing", "in", "general", "practice.", "The", "odds", "ratio", "for", "an", "increase", "in", "testing", "in", "the", "intervention", "group", "compared", "to", "the", "control", "group", "was", "0.9", "(95%", "CI:", "0.6,", "1.2).", "Major", "barriers", "to", "increased", "chlamydia", "testing", "reported", "by", "GPs", "included", "a", "lack", "of", "time,", "difficulty", "in", "remembering", "to", "offer", "testing", "and", "a", "lack", "of", "patient", "awareness", "around", "testing.", "Conclusions:", "A", "small", "financial", "incentive", "alone", "did", "not", "increase", "chlamydia", "testing", "among", "young", "women", "attending", "general", "practice.", "It", "is", "possible", "small", "incentive", "payments", "in", "conjunction", "with", "reminder", "and", "feedback", "systems", "may", "be", "effective,", "as", "may", "higher", "financial", "incentive", "payments.", "Further", "research", "is", "required", "to", "determine", "if", "financial", "incentives", "can", "increase", "testing", "in", "Australian", "general", "practice,", "the", "type", "and", "level", "of", "financial", "scheme", "required", "and", "whether", "incentives", "needs", "to", "be", "part", "of", "a", "multi-faceted", "package.", "Trial", "Registration:", "Australian", "New", "Zealand", "Clinical", "Trial", "Registry", "ACTRN12608000499381.", "Background", "Chlamydia", "trachomatis", "is", "the", "most", "commonly", "notified", "bacterial", "sexually", "transmitted", "infection", "(STI)", "in", "Austra-", "lia,", "with", "notification", "rates", "rising", "nearly", "fourfold", "over", "the", "past", "ten", "years,", "from", "73.5", "per", "100,000", "in", "1999", "to", "273.8", "per", "100,000", "in", "2008", "[1].", "Left", "untreated,", "chlamydia", "can", "*", "Correspondence:", "jbilardi@mshc.org.au", "1Sexual", "Health", "Unit,", "Melbourne", "School", "of", "Population", "Health,", "The", "University", "of", "Melbourne,", "Carlton,", "Victoria", "3053,", "Australia", "lead", "to", "serious", "reproductive", "sequelae", "including", "pelvic", "inflammatory", "disease,", "ectopic", "pregnancy", "and", "infertility", "[2,3].", "Given", "that", "up", "to", "90%", "of", "infections", "are", "asympto-", "matic", "[3],", "increased", "testing", "is", "required", "to", "effectively", "detect", "and", "control", "chlamydia", "infection", "and", "limit", "its", "associated", "morbidity.", "In", "Australia,", "national", "chlamydia", "testing", "guidelines", "issued", "by", "the", "Royal", "Australian", "College", "of", "General", "Prac-", "titioners", "(RACGP)", "[4]", "recommend", "annual", "testing", "of", "©", "2010", "Bilardi", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Shi", "et", "al.", "BMC", "Biotechnology", "2011,", "11:77", "http://www.biomedcentral.com/1472-6750/11/77", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "The", "generation", "and", "evaluation", "of", "recombinant", "human", "IgA", "specific", "for", "Plasmodium", "falciparum", "merozoite", "surface", "protein", "1-19", "(PfMSP1", ")", "19", "Jianguo", "Shi1,", "Richard", "S", "McIntosh1,", "Jaime", "Adame-Gallegos1,", "Prabhjyot", "K", "Dehal2,", "Marjolein", "van", "Egmond3,", "Jan", "van", "de", "Winkel4,", "Simon", "J", "Draper5,", "Emily", "K", "Forbes5,", "Patrick", "H", "Corran6,", "Anthony", "A", "Holder7,", "Jenny", "M", "Woof2", "and", "Richard", "J", "Pleass1*", "Abstract", "Background:", "Human", "immunoglobulin", "G", "(IgG)", "plays", "an", "important", "role", "in", "mediating", "protective", "immune", "responses", "to", "malaria.", "Although", "human", "serum", "immunoglobulin", "A", "(IgA)", "is", "the", "second", "most", "abundant", "class", "of", "antibody", "in", "the", "circulation,", "its", "contribution,", "if", "any,", "to", "protective", "responses", "against", "malaria", "is", "not", "clear.", "Results:", "To", "explore", "the", "mechanism(s)", "by", "which", "IgA", "may", "mediate", "a", "protective", "effect,", "we", "generated", "fully", "human", "IgA", "specific", "for", "the", "C-terminal", "19-kDa", "region", "of", "Plasmodium", "falciparum", "merozoite", "surface", "protein", "1", "(PfMSP119),", "a", "major", "target", "of", "protective", "immune", "responses.", "This", "novel", "human", "IgA", "bound", "antigen", "with", "an", "affinity", "comparable", "to", "that", "seen", "for", "an", "epitope-matched", "protective", "human", "IgG1.", "Furthermore,", "the", "human", "IgA", "induced", "significantly", "higher", "NADPH-mediated", "oxidative", "bursts", "and", "degranulation", "from", "human", "neutrophils", "than", "the", "epitope-matched", "human", "IgG1", "from", "which", "it", "was", "derived.", "Despite", "showing", "efficacy", "in", "in", "vitro", "functional", "assays,", "the", "human", "IgA", "failed", "to", "protect", "against", "parasite", "challenge", "in", "vivo", "in", "mice", "transgenic", "for", "the", "human", "Fca", "receptor", "(FcaRI/CD89).", "A", "minority", "of", "the", "animals", "treated", "with", "IgA,", "irrespective", "of", "FcaRI", "expression,", "showed", "elevated", "serum", "TNF-a", "levels", "and", "concomitant", "mouse", "anti-human", "antibody", "(MAHA)", "responses.", "Conclusions:", "The", "lack", "of", "protection", "afforded", "by", "MSP119-specific", "IgA", "against", "parasite", "challenge", "in", "mice", "transgenic", "for", "human", "FcaRI", "suggests", "that", "this", "antibody", "class", "does", "not", "play", "a", "major", "role", "in", "control", "of", "infection.", "However,", "we", "cannot", "exclude", "the", "possibility", "that", "protective", "capacity", "may", "have", "been", "compromised", "in", "this", "model", "due", "to", "rapid", "clearance", "and", "inappropriate", "bio-distribution", "of", "IgA,", "and", "differences", "in", "FcaRI", "expression", "profile", "between", "humans", "and", "transgenic", "mice.", "Background", "There", "is", "increasing", "interest", "in", "exploring", "the", "therapeutic", "potential", "of", "alternative", "antibody", "(Ab)", "classes", "to", "IgG,", "which", "to", "date", "has", "been", "the", "most", "popular", "choice,", "with", "over", "160", "examples", "currently", "in", "clinical", "trials", "for", "the", "treatment", "of", "diverse", "cancers,", "infectious", "diseases", "and", "auto-immune", "conditions", "[1,2].", "We", "recently", "developed", "a", "novel", "humanized", "mouse", "model", "to", "show", "that", "human", "IgG1", "specific", "for", "Plasmodium", "falciparum", "merozoite", "sur-", "face", "protein", "1-19", "(PfMSP119)", "could", "protect", "animals", "from", "malaria", "in", "passive", "transfer", "experiments", "[3].", "*", "Correspondence:", "richard.pleass@liv.ac.uk", "1Institute", "of", "Genetics,", "Queen’s", "Medical", "Centre,", "University", "of", "Nottingham,", "NG7", "2UH,", "UK", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "However", "there", "are", "numerous", "drawbacks", "to", "using", "IgG-", "based", "therapies", "in", "malaria,", "including", "competition", "for", "FcR", "binding,", "from", "high", "levels", "of", "parasite-induced", "non-", "specific", "IgG", "[4],", "that", "warrant", "the", "exploration", "of", "other", "serum", "Ab", "classes", "for", "use", "against", "infections", "of", "blood.", "FcaRI", "(CD89)", "targeting", "with", "IgA", "could", "offer", "potential", "for", "controlling", "malaria", "with", "therapeutic", "antibodies", "[5].", "Unlike", "IgM,", "IgG", "and", "IgE,", "which", "are", "implicated", "in", "immune", "evasion", "[6],", "placental", "malaria", "[7]", "and", "severe", "malaria", "respectively", "[8],", "IgA", "has", "not", "been", "implicated", "in", "malaria", "pathology,", "arguing", "for", "its", "consideration", "in", "Ab", "therapy.", "Although", "a", "direct", "role", "for", "murine", "IgA", "in", "killing", "of", "rodent", "malaria", "parasites", "has", "not", "been", "investigated", "in", "vivo", "because", "mice", "lack", "an", "equivalent", "of", "human", "FcaRI,", "Plasmodium-specific", "IgA", "has", "been", "detected", "at", "high", "©", "2011", "Shi", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "BMC", "Proceedings", "Proceedings", "Detecting", "population", "stratification", "using", "related", "individuals", "Anthony", "L", "Hinrichs*1,", "Robert", "Culverhouse2,", "Carol", "H", "Jin1", "and", "Brian", "K", "Suarez1,3", "BioMed", "Central", "Open", "Access", "Addresses:", "1Department", "of", "Psychiatry,", "Washington", "University", "School", "of", "Medicine,", "660", "South", "Euclid,", "Campus", "Box", "8134,", "St.", "Louis,", "Missouri", "63110", "USA,", "2Department", "of", "Medicine,", "Washington", "University", "School", "of", "Medicine,", "660", "South", "Euclid,", "St.", "Louis,", "Missouri", "63110", "USA", "and", "3Department", "of", "Genetics,", "Washington", "University", "School", "of", "Medicine,", "660", "South", "Euclid,", "St.", "Louis,", "Missouri", "63110", "USA", "E-mail:", "Anthony", "L", "Hinrichs*", "-", "tony@silver.wustl.edu;", "Robert", "Culverhouse", "-", "rculverh@im.wustl.edu;", "Carol", "H", "Jin", "-", "carolj@nackles.wustl.edu;", "Brian", "K", "Suarez", "-", "bks@themfs.wustl.edu", "*Corresponding", "author", "from", "Genetic", "Analysis", "Workshop", "16", "St", "Louis,", "MO,", "USA", "17-20", "September", "2009", "Published:", "15", "December", "2009", "BMC", "Proceedings", "2009,", "3(Suppl", "7):S106", "doi:", "10.1186/1753-6561-3-S7-S106", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1753-6561/3/S7/S106", "©", "2009", "Hinrichs", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Although", "identification", "of", "cryptic", "population", "stratification", "is", "necessary", "for", "case/control", "association", "analyses,", "it", "is", "also", "vital", "for", "linkage", "analyses", "and", "family-based", "association", "tests", "when", "founder", "genotypes", "are", "missing.", "However,", "including", "related", "individuals", "in", "an", "analysis", "such", "as", "EIGENSTRAT", "can", "result", "in", "bias;", "using", "only", "founders", "or", "one", "individual", "per", "pedigree", "results", "in", "loss", "of", "data", "and", "inaccurate", "estimates", "of", "stratification.", "We", "examine", "a", "generalization", "of", "principal-component", "analyses", "to", "allow", "for", "the", "inclusion", "of", "related", "individuals", "by", "down-weighting", "the", "significance", "of", "individual", "comparisons.", "Background", "At", "the", "heart", "of", "all", "genetic", "case/control", "association", "analyses", "lies", "estimation", "of", "allele", "frequencies.", "For", "linkage", "analyses", "and", "pedigree-based", "association", "analyses,", "allele", "frequency", "estimates", "are", "used", "when", "a", "parental", "genotype", "is", "missing.", "Because", "cryptic", "population", "stratification", "results", "in", "misestimates", "of", "allele", "frequency,", "this", "can", "lead", "to", "false", "positives", "for", "any", "type", "of", "analysis", "with", "missing", "founder", "genotypes", "[1,2].", "Current", "methods", "for", "identifying", "and", "controlling", "population", "stratification", "rely", "on", "unrelated", "individuals.", "When", "they", "are", "applied", "to", "pedigree", "data,", "only", "the", "founders", "are", "analyzed.", "This", "suggests", "that", "the", "situation", "in", "which", "detection", "of", "population", "stratification", "is", "most", "needed", "is", "the", "least", "tractable", "with", "current", "methods.", "Several", "methods", "for", "detecting", "population", "stratification", "exist.", "Two", "of", "the", "most", "common", "methods", "are", "imple-", "mented", "in", "STRUCTURE", "and", "EIGENSTRAT", "[3,4].", "The", "program", "STRUCTURE", "uses", "a", "Markov-chain", "Monte", "Carlo", "(MCMC)", "method", "to", "identify", "natural", "population", "clusters", "based", "on", "multilocus", "genotypes.", "It", "provides", "probability", "of", "membership", "for", "each", "sample", "that", "provides", "a", "very", "natural", "interpretation.", "However,", "it", "is", "too", "computation-", "ally", "intensive", "to", "be", "used", "on", "genome-wide", "association", "study", "(GWAS)", "data", "involving", "hundreds", "of", "thousands", "or", "millions", "of", "markers", "[4].", "To", "handle", "this", "volume", "of", "data,", "a", "more", "computationally", "simple", "method", "is", "required.", "The", "program", "EIGENSTRAT", "uses", "a", "very", "fast", "linear", "algorithm", "to", "identify", "population", "structure.", "In", "particular,", "it", "Page", "1", "of", "4", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Lu", "et", "al.", "BMC", "Bioinformatics", "2011,", "12(Suppl", "8):S2", "http://www.biomedcentral.com/1471-2105/12/S8/S2", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "The", "gene", "normalization", "task", "in", "BioCreative", "III", "Zhiyong", "Lu1*,", "Hung-Yu", "Kao2,", "Chih-Hsuan", "Wei2,", "Minlie", "Huang3,", "Jingchen", "Liu3,", "Cheng-Ju", "Kuo4,", "Chun-Nan", "Hsu4,5,", "Richard", "Tzong-Han", "Tsai6,", "Hong-Jie", "Dai7,8,", "Naoaki", "Okazaki9,", "Han-Cheol", "Cho10,", "Martin", "Gerner11,", "Illes", "Solt12,", "Shashank", "Agarwal13,", "Feifan", "Liu13,", "Dina", "Vishnyakova14,", "Patrick", "Ruch15,", "Martin", "Romacker16,", "Fabio", "Rinaldi17,", "Sanmitra", "Bhattacharya18,", "Padmini", "Srinivasan18,", "Hongfang", "Liu19,", "Manabu", "Torii20,", "Sergio", "Matos21,", "David", "Campos21,", "Karin", "Verspoor22,", "Kevin", "M", "Livingston22,", "W", "John", "Wilbur1*", "From", "The", "Third", "BioCreative", "–", "Critical", "Assessment", "of", "Information", "Extraction", "in", "Biology", "Challenge", "Bethesda,", "MD,", "USA.", "13-15", "September", "2010", "Abstract", "Background:", "We", "report", "the", "Gene", "Normalization", "(GN)", "challenge", "in", "BioCreative", "III", "where", "participating", "teams", "were", "asked", "to", "return", "a", "ranked", "list", "of", "identifiers", "of", "the", "genes", "detected", "in", "full-text", "articles.", "For", "training,", "32", "fully", "and", "500", "partially", "annotated", "articles", "were", "prepared.", "A", "total", "of", "507", "articles", "were", "selected", "as", "the", "test", "set.", "Due", "to", "the", "high", "annotation", "cost,", "it", "was", "not", "feasible", "to", "obtain", "gold-standard", "human", "annotations", "for", "all", "test", "articles.", "Instead,", "we", "developed", "an", "Expectation", "Maximization", "(EM)", "algorithm", "approach", "for", "choosing", "a", "small", "number", "of", "test", "articles", "for", "manual", "annotation", "that", "were", "most", "capable", "of", "differentiating", "team", "performance.", "Moreover,", "the", "same", "algorithm", "was", "subsequently", "used", "for", "inferring", "ground", "truth", "based", "solely", "on", "team", "submissions.", "We", "report", "team", "performance", "on", "both", "gold", "standard", "and", "inferred", "ground", "truth", "using", "a", "newly", "proposed", "metric", "called", "Threshold", "Average", "Precision", "(TAP-k).", "Results:", "We", "received", "a", "total", "of", "37", "runs", "from", "14", "different", "teams", "for", "the", "task.", "When", "evaluated", "using", "the", "gold-", "standard", "annotations", "of", "the", "50", "articles,", "the", "highest", "TAP-k", "scores", "were", "0.3297", "(k=5),", "0.3538", "(k=10),", "and", "0.3535", "(k=20),", "respectively.", "Higher", "TAP-k", "scores", "of", "0.4916", "(k=5,", "10,", "20)", "were", "observed", "when", "evaluated", "using", "the", "inferred", "ground", "truth", "over", "the", "full", "test", "set.", "When", "combining", "team", "results", "using", "machine", "learning,", "the", "best", "composite", "system", "achieved", "TAP-k", "scores", "of", "0.3707", "(k=5),", "0.4311", "(k=10),", "and", "0.4477", "(k=20)", "on", "the", "gold", "standard,", "representing", "improvements", "of", "12.4%,", "21.8%,", "and", "26.6%", "over", "the", "best", "team", "results,", "respectively.", "Conclusions:", "By", "using", "full", "text", "and", "being", "species", "non-specific,", "the", "GN", "task", "in", "BioCreative", "III", "has", "moved", "closer", "to", "a", "real", "literature", "curation", "task", "than", "similar", "tasks", "in", "the", "past", "and", "presents", "additional", "challenges", "for", "the", "text", "mining", "community,", "as", "revealed", "in", "the", "overall", "team", "results.", "By", "evaluating", "teams", "using", "the", "gold", "standard,", "we", "show", "that", "the", "EM", "algorithm", "allows", "team", "submissions", "to", "be", "differentiated", "while", "keeping", "the", "manual", "annotation", "effort", "feasible.", "Using", "the", "inferred", "ground", "truth", "we", "show", "measures", "of", "comparative", "performance", "between", "teams.", "Finally,", "by", "comparing", "team", "rankings", "on", "gold", "standard", "vs.", "inferred", "ground", "truth,", "we", "further", "demonstrate", "that", "the", "inferred", "ground", "truth", "is", "as", "effective", "as", "the", "gold", "standard", "for", "detecting", "good", "team", "performance.", "Background", "The", "gene", "normalization", "(GN)", "task", "in", "BioCreative", "III", "is", "similar", "to", "past", "GN", "tasks", "in", "BioCreative", "I", "and", "[1-3]", "in", "that", "the", "goal", "is", "to", "link", "genes", "or", "gene", "products", "men-", "tioned", "in", "the", "literature", "to", "standard", "database", "identifiers.", "This", "task", "has", "been", "inspired", "in", "part", "by", "a", "pressing", "need", "*", "Correspondence:", "zhiyong.lu@nih.gov;", "wilbur@ncbi.nlm.nih.gov", "1National", "Center", "for", "Biotechnology", "Information", "(NCBI),", "8600", "Rockville", "Pike,", "Bethesda,", "Maryland", "20894,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "to", "assist", "model", "organism", "database", "(MOD)", "literature", "curation", "efforts,", "which", "typically", "involve", "identifying", "and", "normalizing", "genes", "being", "studied", "in", "an", "article.", "For", "instance,", "Mouse", "Genome", "Informatics", "recently", "reported", "their", "search", "and", "evaluation", "of", "potential", "automatic", "tools", "for", "accelerating", "this", "gene", "finding", "process", "[4].", "Specifically,", "this", "year’s", "GN", "task", "was", "to", "have", "participat-", "ing", "systems", "return", "a", "list", "of", "gene", "database", "(Entrez", "Gene", "in", "this", "case)", "identifiers", "for", "a", "given", "article.", "There", "are", "two", "differences", "from", "the", "past", "BioCreative", "GN", "challenges:", "©", "2011", "Lu", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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"even", "during", "interphase", "(Stevens", "1908;", "Metz", "1916;", "Csink", "and", "Henikoff", "1998;", "McKee", "2004).", "In", "some", "cases,", "transvection", "occurs", "when", "the", "enhancer", "of", "one", "copy", "of", "a", "gene", "regulates", "expression", "of", "the", "paired", "copy", "of", "the", "gene", "in", "trans.", "Most", "examples", "of", "transvection", "were", "discov-", "ered", "as", "cases", "of", "intragenic", "complementation,", "in", "which", "two", "Copyright", "©", "2012", "by", "the", "Genetics", "Society", "of", "America", "doi:", "10.1534/genetics.112.140475", "Manuscript", "received", "March", "14,", "2012;", "accepted", "for", "publication", "May", "16,", "2012", "Available", "freely", "online", "through", "the", "author-supported", "open", "access", "option.", "Supporting", "information", "is", "available", "online", "at", "http://www.genetics.org/content/", "suppl/2012/05/25/genetics.112.140475.DC1.", "1Corresponding", "author:", "19700", "Helix", "Dr.,", "Ashburn,", "VA", "20147.", "E-mail:", "mellertd@janelia.", "hhmi.org", "hypomorphic", "or", "loss-of-function", "alleles", "of", "a", "gene", "exhibit", "pairing-dependent", "complementation.", "Because", "of", "the", "low", "frequency", "of", "finding", "such", "complementary", "mutations,", "work", "on", "understanding", "transvection", "has", "focused", "on", "test", "cases", "in-", "cluding,", "but", "not", "limited", "to,", "the", "yellow", "(Geyer", "et", "al.", "1990),", "Ultrabithorax", "(Lewis", "1954),", "and", "white", "loci", "(Jack", "and", "Judd", "1979;", "Gelbart", "and", "Wu", "1982).", "Despite", "the", "limited", "number", "of", "gene", "loci", "amenable", "to", "transvection", "studies,", "several", "important", "features", "of", "its", "un-", "derlying", "mechanism", "have", "been", "elucidated.", "For", "example,", "it", "has", "been", "established", "that", "enhancers", "of", "a", "gene", "more", "strongly", "activate", "transcription", "of", "the", "paired", "copy", "in", "trans", "if", "the", "cis", "core", "promoter", "is", "weakened", "or", "removed", "(Martínez-Laborda", "et", "al.", "1992;", "Morris", "et", "al.", "1999,", "2004;", "Lee", "and", "Wu", "2006;", "Gohl", "et", "al.", "2008).", "Transvection", "may", "also", "be", "modified", "by", "zeste", "(Jack", "and", "Judd", "1979),", "which", "has", "been", "found", "to", "be", "required", "for", "some", "examples", "of", "transvection", "(Kaufman", "et", "al.", "1973;", "Gelbart", "and", "Wu", "1982;", "Leiserson", "et", "al.", "1994),", "and", "may", "fa-", "cilitate", "physical", "interactions", "between", "alleles", "at", "some", "loci", "(Benson", "and", "Pirrotta", "1988;", "Bickel", "and", "Pirrotta", "1990).", "Fi-", "nally,", "the", "genome", "appears", "to", "be", "generally", "permissive", "for", "transvection", "(Chen", "et", "al.", "2002),", "so", "it", "is", "likely", "that", "many", "more", "genes", "undergo", "transvection", "than", "those", "that", "have", "been", "identified", "based", "on", "intragenic", "complementation.", "The", "possible", "widespread", "nature", "of", "transvection", "presents", "a", "potential", "problem", "for", "transgene", "usage", "in", "Drosophila,", "spe-", "cifically", "with", "regard", "to", "site-specific", "integration", "using", "the", "Genetics,", "Vol.", "191,", "1129–1141", "August", "2012", "1129" ]

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[ "Möllerström", "et", "al.", "BMC", "Cancer", "2010,", "10:296", "http://www.biomedcentral.com/1471-2407/10/296", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "RUespea-rcrheargticulelation", "of", "cell", "cycle", "arrest", "protein", "BTG2", "correlates", "with", "increased", "overall", "survival", "in", "breast", "cancer,", "as", "detected", "by", "immunohistochemistry", "using", "tissue", "microarray", "Elin", "Möllerström*1,", "Anikó", "Kovács2,", "Kristina", "Lövgren3,", "Szilard", "Nemes4,", "Ulla", "Delle1,", "Anna", "Danielsson1,", "Toshima", "Parris1,", "Donal", "J", "Brennan5,", "Karin", "Jirström6,", "Per", "Karlsson7", "and", "Khalil", "Helou1", "Abstract", "Background:", "Previous", "studies", "have", "shown", "that", "the", "ADIPOR1,", "ADORA1,", "BTG2", "and", "CD46", "genes", "differ", "significantly", "between", "long-term", "survivors", "of", "breast", "cancer", "and", "deceased", "patients,", "both", "in", "levels", "of", "gene", "expression", "and", "DNA", "copy", "numbers.", "The", "aim", "of", "this", "study", "was", "to", "characterize", "the", "expression", "of", "the", "corresponding", "proteins", "in", "breast", "carcinoma", "and", "to", "determine", "their", "correlation", "with", "clinical", "outcome.", "Methods:", "Protein", "expression", "was", "evaluated", "using", "immunohistochemistry", "in", "an", "independent", "breast", "cancer", "cohort", "of", "144", "samples", "represented", "on", "tissue", "microarrays.", "Fisher's", "exact", "test", "was", "used", "to", "analyze", "the", "differences", "in", "protein", "expression", "between", "dead", "and", "alive", "patients.", "We", "used", "Cox-regression", "multivariate", "analysis", "to", "assess", "whether", "the", "new", "markers", "predict", "the", "survival", "status", "of", "the", "patients", "better", "than", "the", "currently", "used", "markers.", "Results:", "BTG2", "expression", "was", "demonstrated", "in", "a", "significantly", "lower", "proportion", "of", "samples", "from", "dead", "patients", "compared", "to", "alive", "patients,", "both", "in", "overall", "expression", "(P", "=", "0.026)", "and", "cell", "membrane", "specific", "expression", "(P", "=", "0.013),", "whereas", "neither", "ADIPOR1,", "ADORA1", "nor", "CD46", "showed", "differential", "expression", "in", "the", "two", "survival", "groups.", "Furthermore,", "a", "multivariate", "analysis", "showed", "that", "a", "model", "containing", "BTG2", "expression", "in", "combination", "with", "HER2", "and", "Ki67", "expression", "along", "with", "patient", "age", "performed", "better", "than", "a", "model", "containing", "the", "currently", "used", "prognostic", "markers", "(tumour", "size,", "nodal", "status,", "HER2", "expression,", "hormone", "receptor", "status,", "histological", "grade,", "and", "patient", "age).", "Interestingly,", "BTG2", "has", "previously", "been", "described", "as", "a", "tumour", "suppressor", "gene", "involved", "in", "cell", "cycle", "arrest", "and", "p53", "signalling.", "Conclusions:", "We", "conclude", "that", "high-level", "BTG2", "protein", "expression", "correlates", "with", "prolonged", "survival", "in", "patients", "with", "breast", "carcinoma.", "Background", "Breast", "cancer", "is", "the", "most", "common", "malignancy", "among", "women,", "and", "accounted", "for", "approximately", "1.15", "million", "new", "cases", "and", "411,000", "deaths", "worldwide", "in", "2002", "[1].", "During", "the", "last", "decade,", "the", "survival", "rate", "for", "breast", "cancer", "patients", "has", "increased", "dramatically", "due", "to", "earlier", "detec-", "tion", "and", "new", "treatment", "protocols", "[2].", "Presently,", "various", "clinical", "and", "pathological", "markers", "including", "axillary", "lymph", "node", "status,", "hormone", "receptor", "status,", "histological", "*", "Correspondence:", "elin.mollerstrom@neuro.gu.se", "1", "Department", "of", "Oncology,", "Institute", "of", "Clinical", "Sciences,", "Blå", "stråket", "2,", "University", "of", "Gothenburg,", "SE-413", "45", "Göteborg,", "Sweden", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "grade,", "tumour", "size,", "patient", "age,", "HER2", "expression", "and", "vascular", "invasion", "are", "used", "to", "predict", "breast", "cancer", "prog-", "nosis", "and", "provide", "accurate", "treatment", "[3].", "However,", "these", "markers", "are", "insufficient", "and", "approximately", "20", "to", "30%", "of", "breast", "cancer", "patients", "will", "die", "from", "the", "disease", "within", "five", "years", "of", "diagnosis", "[4].", "It", "is,", "therefore,", "of", "great", "importance", "to", "identify", "novel", "molecular", "markers", "to", "further", "refine", "prognosis", "and", "response", "to", "treatment.", "Gene", "expression", "analysis", "has", "been", "used", "to", "develop", "gene", "expression", "signa-", "tures", "that", "predict", "clinical", "outcome", "in", "breast", "cancer", "patients", "[5-9].", "Previously,", "we", "analysed", "breast", "tumours", "from", "lymph", "node-negative", "patients", "using", "gene", "expression", "microarray", "and", "array-CGH", "to", "identify", "genes", "with", "altered", "©", "2010", "Möllerström", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Com-", "mons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduc-", "tion", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Eur", "Radiol", "(2011)", "21:875–881", "DOI", "10.1007/s00330-010-1952-y", "NEURO", "Distribution", "of", "cerebral", "blood", "flow", "in", "the", "caudate", "nucleus,", "lentiform", "nucleus", "and", "thalamus", "in", "patients", "with", "carotid", "artery", "stenosis", "Nolan", "S.", "Hartkamp", "&", "Reinoud", "P.", "H.", "Bokkers", "&", "H.", "Bart", "van", "der", "Worp", "&", "M.", "J.", "P.", "van", "Osch", "&", "L.", "Jaap", "Kappelle", "&", "Jeroen", "Hendrikse", "Received:", "24", "May", "2010", "/", "Revised:", "1", "August", "2010", "/", "Accepted:", "17", "August", "2010", "/", "Published", "online:", "18", "September", "2010", "#", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Objective", "To", "investigate", "the", "influence", "of", "internal", "carotid", "artery", "(ICA)", "stenosis", "on", "the", "distribution", "of", "blood", "flow", "to", "the", "caudate", "nucleus,", "lentiform", "nucleus,", "and", "thalamus.", "Methods", "We", "studied", "18", "healthy", "control", "subjects,", "20", "patients", "with", "a", "unilateral", "asymptomatic", "ICA", "stenosis,", "and", "15", "patients", "with", "a", "recently", "symptomatic", "unilateral", "ICA", "stenosis.", "The", "contribution", "of", "the", "ICAs", "and", "the", "basilar", "artery", "to", "the", "perfusion", "of", "the", "deep", "brain", "structures", "was", "assessed", "by", "perfusion", "territory", "selective", "arterial", "spin", "labeling", "(ASL)", "MRI.", "Differences", "were", "tested", "with", "a", "two-tailed", "Fishers’", "exact", "test.", "Results", "The", "caudate", "nucleus", "was", "predominantly", "supplied", "with", "blood", "by", "the", "ipsilateral", "ICA", "in", "all", "groups.", "In", "4", "of", "the", "15", "(27%)", "the", "symptomatic", "patients,", "the", "caudate", "nucleus", "partially", "received", "blood", "from", "the", "contralateral", "ICA,", "compared", "to", "none", "of", "the", "18", "healthy", "control", "subjects", "(p", "=", "0.03).", "The", "lentiform", "nucleus", "and", "the", "thalamus", "were", "predominantly", "supplied", "with", "blood", "by", "the", "ipsilateral", "ICA", "and", "basilar", "artery", "respectively", "in", "all", "groups.", "N.", "S.", "Hartkamp", "(*)", ":", "R.", "P.", "H.", "Bokkers", ":", "J.", "Hendrikse", "Department", "of", "Radiology,", "University", "Medical", "Center", "Utrecht,", "PO", "Box", "85500,", "3508", "GA", "Utrecht,", "The", "Netherlands", "e-mail:", "n.s.hartkamp@umcutrecht.nl", "H.", "B.", "van", "der", "Worp", ":", "L.", "J.", "Kappelle", "Department", "of", "Neurology,", "Rudolf", "Magnus", "Institute", "of", "Neuroscience,", "University", "Medical", "Center", "Utrecht,", "Utrecht,", "The", "Netherlands", "M.", "J.", "P.", "van", "Osch", "Department", "of", "Radiology,", "C.J.", "Gorter", "Institute", "of", "High", "Field", "MRI,", "Leiden", "University", "Medical", "Center,", "Leiden,", "The", "Netherlands", "Conclusion", "In", "patients", "with", "a", "symptomatic", "ICA", "stenosis,", "the", "caudate", "nucleus", "may", "be", "supplied", "with", "blood", "by", "the", "contralateral", "ICA", "more", "often", "than", "in", "healthy", "controls.", "Keywords", "Magnetic", "resonance", "imaging", ".", "Cerebral", "hemodynamics", ".", "Perfusion", ".", "Basal", "ganglia", ".", "Carotid", "artery", "stenosis", "Introduction", "There", "is", "wide", "variation", "in", "the", "perfusion", "territories", "of", "the", "brain-feeding", "arteries,", "which", "is", "most", "pronounced", "in", "those", "supplying", "the", "deep", "brain", "structures", "[1–3].", "The", "caudate", "nucleus,", "lentiform", "nucleus,", "and", "thalamus", "are", "supplied", "with", "blood", "from", "groups", "of", "different", "perforating", "arteries", "that", "branch", "either", "from", "the", "anterior,", "middle", "and", "posterior", "cerebral", "artery", "or", "from", "the", "posterior", "communicating", "artery", "[2,", "4–7].", "In", "addition", "to", "the", "normal", "variability,", "there", "may", "be", "a", "shift", "in", "the", "perfusion", "territories", "of", "the", "brain-feeding", "arteries", "in", "patients", "with", "steno-occlusive", "disease", "of", "the", "ICA,", "due", "to", "the", "recruitment", "of", "collateral", "blood", "pathways", "[8,", "9].", "Perfusion", "territory", "selective", "arterial", "spin", "labeling", "magnetic", "resonance", "imaging", "(ASL-MRI)", "has", "recently", "been", "intro-", "duced", "to", "visualize", "the", "perfusion", "territories", "of", "the", "individual", "brain-feeding", "arteries", "[10,", "11].", "ASL-MRI", "is", "a", "non-invasive", "technique", "for", "imaging", "whole-brain", "cerebral", "perfusion", "that", "uses", "radiofrequency", "pulses", "to", "magnetically", "label", "blood", "and", "does", "not", "require", "gadolinium-based", "contrast", "agents.", "The", "aim", "of", "our", "study", "was", "to", "investigate", "the", "influence", "of", "ICA", "stenosis", "on", "the", "distribution", "of", "cerebral", "blood", "flow", "to", "the", "caudate", "nucleus,", "lentiform", "nucleus", "and", "thalamus", "with", "perfusion", "territory", "selective", "ASL-MRI", "in", "patients", "with" ]

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[ "Abebe", "et", "al.", "BMC", "Public", "Health", "2012,", "12:504", "http://www.biomedcentral.com/1471-2458/12/504", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Tuberculosis", "lymphadenitis", "in", "Southwest", "Ethiopia:", "a", "community", "based", "cross-sectional", "study", "Gemeda", "Abebe1,8*,", "Amare", "Deribew2,8,", "Ludwig", "Apers3,", "Alemseged", "Abdissa1,", "Fetene", "Deribie1,", "Kifle", "Woldemichael2,", "Jaffer", "Shiffa4,", "Markos", "Tesfaye5,", "Chali", "Jira6,", "Mesele", "Bezabih1,", "Abraham", "Aseffa7,", "Alemayehu", "Bekele1", "and", "Robert", "Colebunders3,8", "Abstract", "Background:", "In", "Ethiopia", "where", "there", "is", "no", "strong", "surveillance", "system", "and", "diagnostic", "facilities", "are", "limited,", "the", "real", "burden", "of", "tuberculosis", "(TB)", "lymphadenitis", "is", "not", "well", "known.", "Therefore,", "we", "conducted", "a", "study", "to", "estimate", "the", "prevalence", "of", "TB", "lymphadenitis", "in", "Southwest", "Ethiopia.", "Methods:", "A", "community", "based", "cross-sectional", "study", "was", "conducted", "from", "February", "to", "March", "2009", "in", "the", "Gilgel", "Gibe", "field", "research", "area.", "A", "total", "of", "30,040", "individuals", "15", "years", "or", "older", "in", "10,882", "households", "were", "screened", "for", "TB", "lymphadenitis.", "Any", "individual", "15", "years", "or", "older", "with", "lumps", "in", "the", "neck,", "armpits", "or", "groin", "up", "on", "interview", "were", "considered", "TB", "lymphadenitis", "suspect.", "The", "diagnosis", "of", "TB", "lymphadenitis", "was", "established", "when", "acid", "fast", "bacilli", "(AFB)", "smear", "microscopy", "of", "fine", "needle", "aspiration", "(FNA)", "sample,", "culture", "or", "cytology", "suggested", "TB.", "HIV", "counseling", "and", "testing", "was", "offered", "to", "all", "TB", "lymphadenitis", "suspects.", "Descriptive", "and", "bivariate", "analysis", "was", "done", "using", "SPSS", "version", "15.", "Results:", "Complete", "data", "were", "available", "for", "27,597", "individuals.", "A", "total", "of", "87", "TB", "lymphadenitis", "suspects", "were", "identified.", "Most", "of", "the", "TB", "lymphadenitis", "suspects", "were", "females", "(72.4%).", "Sixteen", "cases", "of", "TB", "lymphadenitis", "were", "confirmed.", "The", "prevalence", "of", "TB", "lymphadenitis", "was", "thus", "58.0", "per", "100,000", "people", "(16/27,597)", "(95%", "CI", "35.7-94.2).", "Individuals", "who", "had", "a", "contact", "history", "with", "chronic", "coughers", "(OR", "5.58,", "95%", "CI", "1.23-25.43)", "were", "more", "likely", "to", "have", "TB", "lymphadenitis.", "Lymph", "nodes", "with", "caseous", "FNA", "were", "more", "likely", "to", "be", "positive", "for", "TB", "lymphadenitis", "(OR", "5.46,", "95%", "CI", "1.69-17.61).", "Conclusion:", "The", "prevalence", "of", "TB", "lymphadenitis", "in", "Gilgel", "Gibe", "is", "similar", "with", "the", "WHO", "estimates", "for", "Ethiopia.", "Screening", "of", "TB", "lymphadenitis", "particularly", "for", "family", "members", "who", "have", "contact", "with", "chronic", "coughers", "is", "recommended.", "Health", "extension", "workers", "could", "be", "trained", "to", "screen", "and", "refer", "TB", "lymphadenitis", "suspects", "using", "simple", "methods.", "Keywords:", "TB", "lymphadenitis,", "Prevalence,", "Jimma,", "Ethiopia", "Background", "TB", "lymphadenitis", "is", "the", "most", "common", "form", "of", "extrapul-", "monary", "TB", "[1].", "Its", "epidemiology", "and", "diagnostic", "aspects", "vary", "according", "to", "the", "patients’", "geographic", "origin", "and", "the", "burden", "of", "TB", "and", "HIV", "infection", "[2].", "Globally", "the", "inci-", "dence", "of", "all", "forms", "of", "TB", "is", "decreasing.", "However,", "the", "rate", "*", "Correspondence:", "gemeda.abebe@ju.edu.et", "1Department", "of", "Medical", "Laboratory", "Sciences", "and", "Pathology,", "Jimma", "University,", "Jimma,", "Ethiopia", "8Department", "of", "Epidemiology", "and", "Social", "Medicine,", "University", "of", "Antwerp,", "Antwerp,", "Belgium", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "is", "not", "similar", "across", "all", "WHO", "regions.", "In", "the", "Africa", "re-", "gion", "it", "is", "decreasing", "slowly", "by", "1.8%", "per", "year", "[3].", "Ethiopia", "is", "among", "the", "22", "high", "TB", "burden", "countries", "in", "the", "world.", "The", "proportion", "of", "extrapulmonary", "TB", "among", "newly", "diagnosed", "TB", "patients", "has", "been", "increasing", "for", "the", "last", "two", "decades", "[3].", "The", "WHO", "and", "the", "Ethiopian", "TB", "control", "program", "estimate", "that", "the", "proportion", "of", "extra-", "pulmonary", "TB", "among", "the", "total", "number", "of", "new", "TB", "cases", "(156,928)", "is", "about", 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[ "Psychopharmacology", "(2010)", "208:469–474", "DOI", "10.1007/s00213-009-1747-5", "ORIGINAL", "INVESTIGATION", "Alcohol", "breaks", "down", "interhemispheric", "inhibition", "in", "females", "but", "not", "in", "males", "Alcohol", "and", "frontal", "connectivity", "Sylco", "S.", "Hoppenbrouwers", "&", "Dennis", "Hofman", "&", "Dennis", "J.", "L.", "G.", "Schutter", "Received:", "8", "October", "2009", "/", "Accepted:", "25", "November", "2009", "/", "Published", "online:", "18", "December", "2009", "#", "The", "Author(s)", "2009.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Introduction", "Alcohol", "has", "renowned", "behavioral", "disinhibi-", "tory", "properties", "which", "are", "suggested", "to", "involve", "reductions", "in", "frontal", "lobe", "functioning", "as", "a", "result", "of", "diminished", "inter-", "hemispheric", "connectivity.", "Methods", "To", "examine", "sex", "differences", "in", "frontal", "interhemi-", "spheric", "connectivity", "in", "response", "to", "alcohol,", "12", "female", "and", "ten", "male", "healthy", "volunteers", "received", "a", "single", "administration", "of", "0.5‰", "alcohol", "in", "a", "placebo-controlled", "counterbalanced", "crossover", "design.", "Paired-pulse", "transcranial", "magnetic", "stim-", "ulation", "was", "applied", "to", "measure", "transcallosal", "inhibition", "(TCI)", "between", "the", "left", "and", "right", "primary", "motor", "cortex", "(M1).", "Results", "Results", "showed", "significant", "reductions", "in", "TCI", "after", "alcohol", "administration", "in", "female", "participants", "exclusively.", "Discussion", "These", "findings", "provide", "the", "first", "evidence", "that", "moderate", "doses", "of", "alcohol", "differentially", "affect", "frontal", "interhemispheric", "connectivity", "in", "males", "and", "females.", "The", "present", "data", "may", "shed", "new", "light", "on", "the", "physiological", "mechanisms", "underlying", "sex", "differences", "in", "the", "susceptibility", "to", "alcohol.", "Keywords", "Alcohol", ".", "Frontal", "cortex", ".", "Interhemispheric", "connectivity", ".", "Transcallosal", "inhibition", ".", "Transcranial", "magnetic", "stimulation", "S.", "S.", "Hoppenbrouwers", "(*)", ":", "D.", "Hofman", ":", "D.", "J.", "L.", "G.", "Schutter", "Department", "of", "Experimental", "Psychology,", "Helmholtz", "Research", "Institute,", "Utrecht", "University,", "Heidelberglaan", "2,", "3584", "CS", "Utrecht,", "The", "Netherlands", "e-mail:", "s.s.hoppenbrouwers@uu.nl", "Introduction", "In", "the", "last", "decades,", "alcohol", "consumption", "steadily", "increased", "culminating", "in", "3.2", "million", "yearly", "deaths", "either", "as", "a", "direct", "or", "indirect", "result", "of", "alcohol", "worldwide", "(World", "Health", "Organi-", "sation", "2004).", "Moderate", "doses", "of", "alcohol", "(≤0.5‰)", "can", "produce", "feelings", "of", "relaxation", "and", "release", "of", "response", "inhibition,", "whereas", "higher", "doses", "of", "alcohol", "(1–1.5‰)", "cause", "impairments", "in", "motor", "coordination", "and", "vision.", "Extremely", "high", "alcohol", "levels", "(≥2.5‰)", "ultimately", "lead", "to", "coma", "and", "death", "(Hieda", "et", "al.", "2005).", "Interestingly,", "the", "effects", "of", "alcohol", "seem", "to", "be", "more", "pronounced", "in", "females", "than", "in", "males", "(Mills", "and", "Bisgrove", "1983;", "Niaura", "et", "al.", "1987;", "Mumenthaler", "et", "al.", "1999;", "Hommer", "2003).", "Sex", "differences", "in", "response", "to", "alcohol", "intake", "can", "in", "part", "be", "explained", "by", "differences", "in", "the", "percentage", "of", "body", "fat", "(Addolorato", "et", "al.", "1999)", "and", "the", "availability", "of", "the", "enzyme", "alcohol", "dehydro-", "genase", "which", "breaks", "down", "alcohol", "(Baraona", "et", "al.", "2001).", "However,", "other", "research", "suggests", "that", "females", "differ", "from", "males", "on", "the", "innate", "physiological", "susceptibility", "to", "the", "central", "effects", "of", "alcohol", "(Hommer", "et", "al.", "1996,", "2001;", "Agartz", "et", "al.", "2003;", "Sasaki", "et", "al.", "2009).", "For", "instance,", "chronic", "misuse", "of", "alcohol", "leaves", "female", "alcoholics", "with", "more", "brain", "damage", "than", "their", "male", "counterparts", "(Hommer", "et", "al.", "2001;", "Hommer", "2003).", "Notably,", "however,", "moderate", "drinking", "habits", "also", "affect", "the", "female", "brain", "more", "strongly", "than", "the", "male", "brain", "(Sasaki", "et", "al.", "2009).", "In", "addition", "to", "the", "general", "effects", "on", "the", "central", "and", "peripheral", "nervous", "system,", "alcohol", "typically", "affects", "frontal", "cortical", "functions", "such", "as", "response", "inhibition", "and", "cognitive", "regulation", "(Jentsch", "and", "Taylor", "1999;", "Lyvers", "2000).", "In", "fact,", "even", "though", "alcohol", "diffuses", "through", "all", "biological", "mem-", "branes", "and", "is", "distributed", "throughout", "the", "body,", "the", "anterior", "cortical", "regions", "of", "the", "brain", "have", "been", "shown", "to", "be", "especially", "vulnerable", "to", "the", "acute", "(Weitlauf", "and", "Woodward" ]

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